Human Gene Module / Chromosome 19 / FAM98C

FAM98Cfamily with sequence similarity 98 member C

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
4 / 4
Rare Variants / Common Variants
5 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
19q13.2
Associated Disorders
-
Relevance to Autism

Transmitted protein-truncating variants (PTVs) in the FAM98C gene were identified in probands from the Autism Sequencing Consortium (De Rubeis et al., 2014), while a de novo splice-site variant and transmitted nonsense variants in this gene were identified in ASD probands from multiplex families from the iHART cohort (Ruzzo et al., 2019). TADA analysis of de novo and transmitted variants from iHART, the Simons Simplex Collection, the Autism Sequencing Consortium, and the Autism Genome Project in Ruzzo et al., 2019 identified FAM98C as an ASD candidate gene with a false discovery rate (FDR) < 0.1.

Molecular Function

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to FAM98C (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
2 Recent Recommendation Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
3 Support - Cirnigliaro M et al. (2023) Yes -
4 Support - Duyen T Bui et al. (2024) Yes -
Rare Variants   (5)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.918+2T>G - splice_site_variant De novo - Multiplex 31398340 Ruzzo EK , et al. (2019)
c.844C>T p.Arg282Ter stop_gained Unknown - Unknown 38287090 Duyen T Bui et al. (2024)
c.790C>T p.Arg264Ter stop_gained Familial Paternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.1045A>T p.Lys349Ter stop_gained Familial Maternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.46C>T p.Gln16Ter stop_gained Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Transmitted protein-truncating variants (PTVs) in the FAM98C gene were identified in probands from the Autism Sequencing Consortium (De Rubeis et al., 2014), while a de novo splice-site variant and transmitted nonsense variants in this gene were identified in ASD probands from multiplex families from the iHART cohort (Ruzzo et al., 2019). TADA analysis of de novo and transmitted variants from iHART, the Simons Simplex Collection, the Autism Sequencing Consortium, and the Autism Genome Project in Ruzzo et al., 2019 identified FAM98C as an ASD candidate gene with a false discovery rate (FDR) < 0.1.

Score Delta: Score remained at 2

criteria met
See SFARI Gene'scoring criteria
2

Strong Candidate

See all Category 2 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

4/1/2022
3
icon
2

Decreased from 3 to 2

Description

Transmitted protein-truncating variants (PTVs) in the FAM98C gene were identified in probands from the Autism Sequencing Consortium (De Rubeis et al., 2014), while a de novo splice-site variant and transmitted nonsense variants in this gene were identified in ASD probands from multiplex families from the iHART cohort (Ruzzo et al., 2019). TADA analysis of de novo and transmitted variants from iHART, the Simons Simplex Collection, the Autism Sequencing Consortium, and the Autism Genome Project in Ruzzo et al., 2019 identified FAM98C as an ASD candidate gene with a false discovery rate (FDR) < 0.1.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Transmitted protein-truncating variants (PTVs) in the FAM98C gene were identified in probands from the Autism Sequencing Consortium (De Rubeis et al., 2014), while a de novo splice-site variant and transmitted nonsense variants in this gene were identified in ASD probands from multiplex families from the iHART cohort (Ruzzo et al., 2019). TADA analysis of de novo and transmitted variants from iHART, the Simons Simplex Collection, the Autism Sequencing Consortium, and the Autism Genome Project in Ruzzo et al., 2019 identified FAM98C as an ASD candidate gene with a false discovery rate (FDR) < 0.1.

Reports Added
[New Scoring Scheme]
7/1/2019
icon
4

Increased from to 4

Description

Transmitted protein-truncating variants (PTVs) in the FAM98C gene were identified in probands from the Autism Sequencing Consortium (De Rubeis et al., 2014), while a de novo splice-site variant and transmitted nonsense variants in this gene were identified in ASD probands from multiplex families from the iHART cohort (Ruzzo et al., 2019). TADA analysis of de novo and transmitted variants from iHART, the Simons Simplex Collection, the Autism Sequencing Consortium, and the Autism Genome Project in Ruzzo et al., 2019 identified FAM98C as an ASD candidate gene with a false discovery rate (FDR) < 0.1.

Krishnan Probability Score

Score 0.39814461376343

Ranking 23456/25841 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 3.566522831586E-10

Ranking 16768/18225 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 0.78997650105038

Ranking 2045/18665 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 0.17377178381908

Ranking 4741/20870 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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