Human Gene Module / Chromosome 12 / C12orf57

C12orf57Chromosome 12 open reading frame 57

SFARI Gene Score
S
Syndromic Syndromic
Autism Reports / Total Reports
3 / 15
Rare Variants / Common Variants
30 / 0
Aliases
C12orf57, C10,  GRCC10,  TEMTYS
Associated Syndromes
Temtamy syndrome, Temtamy syndrome, ASD, DD, ID
Chromosome Band
12p13.31
Associated Disorders
DD/NDD, ID, EPS, ASD
Relevance to Autism

The same homozygous variant in the C12orf57 gene (c.1A>G; p.Met1?) was detected in ten affected individuals from four consanguineous families of Arab descent; all affected individuals presented with developmental delay/intellectual disability, autistic features, and hypoplasia or agenesis of the corpus callosum (Akizu et al., 2013).

Molecular Function

Function unknown; ubiquitously expressed in human tissues, with high expression in fetal brain. Temtamy syndrome (OMIM:218340), which is characterized by mental retardation with or without craniofacial dysmorphism, ocular coloboma, or abnormal corpus callosum, can be caused by homozygous or compound heterozygous mutation in the C12ORF57 gene.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to C12orf57 (15 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Mutations in c12orf57 cause a syndromic form of colobomatous microphthalmia Zahrani F , et al. (2013) No Epilepsy/seizures
2 Primary Whole-exome sequencing identifies mutated c12orf57 in recessive corpus callosum hypoplasia Akizu N , et al. (2013) No Epilepsy/seizures
3 Support A newly recognized autosomal recessive syndrome affecting neurologic function and vision Salih MA , et al. (2013) No Epilepsy/seizures
4 Support Exome sequencing identifies compound heterozygous mutations in C12orf57 in two siblings with severe intellectual disability, hypoplasia of the corpus callosum, chorioretinal coloboma, and intractable seizures Platzer K , et al. (2014) No DD, ID, epilepsy/seizures, autistic behavior
5 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
6 Support Accelerating novel candidate gene discovery in neurogenetic disorders via whole-exome sequencing of prescreened multiplex consanguineous families Alazami AM , et al. (2015) No -
7 Support Exome sequencing in mostly consanguineous Arab families with neurologic disease provides a high potential molecular diagnosis rate Charng WL , et al. (2016) No -
8 Support Clinical exome sequencing: results from 2819 samples reflecting 1000 families Trujillano D , et al. (2016) No ASD
9 Support Diagnostic Yield and Novel Candidate Genes by Exome Sequencing in 152 Consanguineous Families With Neurodevelopmental Disorders Reuter MS , et al. (2017) No ID, hypotonia
10 Recent Recommendation Further delineation of Temtamy syndrome of corpus callosum and ocular abnormalities Alrakaf L , et al. (2018) No Autistic behavior
11 Support Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population Monies D , et al. (2019) No DD, ID, ASD, epilepsy/seizures
12 Support - Zhou X et al. (2022) Yes -
13 Support - Nerakh G et al. (2023) Yes -
14 Support - Bartolomaeus T et al. (2023) No -
15 Support - et al. () No -
Rare Variants   (30)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.373G>A p.Ala125Thr missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.138C>T p.Asp46= synonymous_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.152T>A p.Leu51Gln missense_variant Familial - Simplex 23453665 Zahrani F , et al. (2013)
c.145A>T p.Lys49Ter stop_gained Familial Maternal Simplex 37451886 Nerakh G et al. (2023)
c.1A>G p.Met1? initiator_codon_variant Familial Both parents Multiplex 37799141 et al. ()
c.1A>G p.Met1? initiator_codon_variant Familial - Simplex 23453665 Zahrani F , et al. (2013)
c.184C>T p.Gln62Ter stop_gained Familial Maternal Multiplex 24798461 Platzer K , et al. (2014)
c.53-2A>G - splice_site_variant Familial Both parents Simplex 27435318 Charng WL , et al. (2016)
c.53-2A>G - splice_site_variant Familial Both parents Simplex 29383837 Alrakaf L , et al. (2018)
c.43C>T p.Gln15Ter stop_gained Familial Both parents Multiplex 29383837 Alrakaf L , et al. (2018)
c.53-2A>G - splice_site_variant Familial Both parents Multiplex 29383837 Alrakaf L , et al. (2018)
c.229+2T>C - splice_site_variant Familial Both parents Multiplex 29383837 Alrakaf L , et al. (2018)
c.1A>G p.Met1Val missense_variant Familial Both parents Multiplex 23633300 Salih MA , et al. (2013)
c.1A>G p.Met1? initiator_codon_variant Familial Both parents - 27848944 Trujillano D , et al. (2016)
c.-3_2delinsG - 5_prime_UTR_variant Familial Both parents Multiplex 29383837 Alrakaf L , et al. (2018)
c.1A>G p.Met1? initiator_codon_variant Familial Paternal Multiplex 24798461 Platzer K , et al. (2014)
c.1A>G p.Met1? initiator_codon_variant Familial Both parents Simplex 31130284 Monies D , et al. (2019)
c.1A>G p.Met1? initiator_codon_variant Familial Both parents Unknown 31130284 Monies D , et al. (2019)
c.1A>G p.Met1? initiator_codon_variant Familial Both parents Multiplex 23453666 Akizu N , et al. (2013)
c.1A>G p.Met1? initiator_codon_variant Familial Both parents Simplex 29383837 Alrakaf L , et al. (2018)
c.1A>G p.Met1? initiator_codon_variant Familial Both parents Multiplex 23453665 Zahrani F , et al. (2013)
c.1A>G p.Met1? initiator_codon_variant Familial Both parents Multiplex 28097321 Reuter MS , et al. (2017)
c.1A>G p.Met1? initiator_codon_variant Familial Both parents Multiplex 29383837 Alrakaf L , et al. (2018)
c.1A>G p.Met1? initiator_codon_variant Familial Both parents Multiplex 25558065 Alazami AM , et al. (2015)
c.1A>G p.Met1? initiator_codon_variant Familial Both parents Simplex 27848944 Trujillano D , et al. (2016)
c.224_242del p.Gly75ValfsTer22 frameshift_variant Familial Paternal Simplex 37451886 Nerakh G et al. (2023)
NM_001301836.1:c.14-2A>G - splice_site_variant Familial Both parents Unknown 31130284 Monies D , et al. (2019)
c.1A>G p.Met1? initiator_codon_variant Familial Both parents Multiplex 37460657 Bartolomaeus T et al. (2023)
c.1A>G p.Met1? initiator_codon_variant Familial Both parents Not simplex (positive family history) 31130284 Monies D , et al. (2019)
c.1A>G p.Met1? initiator_codon_variant Familial Both parents Not simplex (positive family history) 27848944 Trujillano D , et al. (2016)
Common Variants  

No common variants reported.

SFARI Gene score
S

Syndromic

Biallelic variants in the C12orf57 gene are responsible for Temtamy syndrome (OMIM 218340), a mental retardation/multiple congenital anomaly syndrome characterized by variable craniofacial dysmorphism, ocular coloboma, seizures, and brain abnormalities, including abnormalities of the corpus callosum and thalamus; ASD or autistic features have been observed in individuals with Temtamy syndrome (Akizu et al., 2013; Platzer et al., 2014; Trujillano et al., 2016). Alrakaf et al., 2018 presented 23 novel individuals with Temtany syndrome and reported that 12 of these cases (52.2%) presented with autistic behavior.

Score Delta: Score remained at S

criteria met
See SFARI Gene'scoring criteria
S

Syndromic

See all Category S Genes

The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."

10/1/2019
S
icon
S

Score remained at S

New Scoring Scheme
Description

Biallelic variants in the C12orf57 gene are responsible for Temtamy syndrome (OMIM 218340), a mental retardation/multiple congenital anomaly syndrome characterized by variable craniofacial dysmorphism, ocular coloboma, seizures, and brain abnormalities, including abnormalities of the corpus callosum and thalamus; ASD or autistic features have been observed in individuals with Temtamy syndrome (Akizu et al., 2013; Platzer et al., 2014; Trujillano et al., 2016). Alrakaf et al., 2018 presented 23 novel individuals with Temtany syndrome and reported that 12 of these cases (52.2%) presented with autistic behavior.

Reports Added
[New Scoring Scheme]
7/1/2019
S
icon
S

Score remained at S

Description

Biallelic variants in the C12orf57 gene are responsible for Temtamy syndrome (OMIM 218340), a mental retardation/multiple congenital anomaly syndrome characterized by variable craniofacial dysmorphism, ocular coloboma, seizures, and brain abnormalities, including abnormalities of the corpus callosum and thalamus; ASD or autistic features have been observed in individuals with Temtamy syndrome (Akizu et al., 2013; Platzer et al., 2014; Trujillano et al., 2016). Alrakaf et al., 2018 presented 23 novel individuals with Temtany syndrome and reported that 12 of these cases (52.2%) presented with autistic behavior.

Reports Added
[Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population.2019]
1/1/2017
S
icon
S

Score remained at S

Description

Biallelic variants in the C12orf57 gene are responsible for Temtamy syndrome (OMIM 218340), a mental retardation/multiple congenital anomaly syndrome characterized by variable craniofacial dysmorphism, ocular coloboma, seizures, and brain abnormalities, including abnormalities of the corpus callosum and thalamus; ASD or autistic features have been observed in individuals with Temtamy syndrome (Akizu et al., 2013; Trujillano et al., 2016).

Reports Added
[Diagnostic Yield and Novel Candidate Genes by Exome Sequencing in 152 Consanguineous Families With Neurodevelopmental Disorders.2017]
10/1/2016
icon
S

Score remained at S

Description

Biallelic variants in the C12orf57 gene are responsible for Temtamy syndrome (OMIM 218340), a mental retardation/multiple congenital anomaly syndrome characterized by variable craniofacial dysmorphism, ocular coloboma, seizures, and brain abnormalities, including abnormalities of the corpus callosum and thalamus; ASD or autistic features have been observed in individuals with Temtamy syndrome (Akizu et al., 2013; Trujillano et al., 2016).

Reports Added
[Clinical exome sequencing: results from 2819 samples reflecting 1000 families.2016]
Krishnan Probability Score

Score 0.33590406732967

Ranking 24380/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
Original Source
ExAC Score

Score 0.060336064482682

Ranking 8367/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Original Source
Sanders TADA Score

Score 0.90508786045036

Ranking 6922/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Original Source
Zhang D Score

Score -0.1880241960924

Ranking 15148/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
Original Source
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