Human Gene Module / Chromosome 2 / TET3

TET3tet methylcytosine dioxygenase 3

SFARI Gene Score
S
Syndromic Syndromic
Autism Reports / Total Reports
1 / 4
Rare Variants / Common Variants
14 / 0
Aliases
TET3, hCG_40738
Associated Syndromes
-
Chromosome Band
2p13.1
Associated Disorders
ASD
Relevance to Autism

Beck et al., 2020 identified and characterized 11 cases of human TET3 deficiency in eight families presenting with common phenotypic features including intellectual disability and/or global developmental delay (11/11), hypotonia (8/11), ASD or autistic features including difficulty with social interactions (6/11), movements disorders (5/11), growth abnormalities (8/11), and facial dysmorphism; included in this cohort was a family with three affected children previously described in Santos-Cortez et al., 2018.

Molecular Function

Members of the ten-eleven translocation (TET) gene family, including TET3, play a role in the DNA methylation process.

SFARI Genomic Platforms
Reports related to TET3 (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Novel candidate genes and variants underlying autosomal recessive neurodevelopmental disorders with intellectual disability Santos-Cortez RLP , et al. (2018) No -
2 Primary Delineation of a Human Mendelian Disorder of the DNA Demethylation Machinery: TET3 Deficiency Beck DB , et al. (2020) No ASD or autistic features
3 Support - Seyama R et al. (2021) No ASD or autistic features, epilepsy/seizures
4 Support - Woodbury-Smith M et al. (2022) Yes -
Rare Variants   (14)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.5083C>T p.Gln1695Ter stop_gained De novo NA - 31928709 Beck DB , et al. (2020)
c.2552C>T p.Thr851Met missense_variant De novo NA - 31928709 Beck DB , et al. (2020)
c.5030C>T p.Pro1677Leu missense_variant De novo NA - 31928709 Beck DB , et al. (2020)
c.2254C>T p.Arg752Cys missense_variant Familial Paternal - 31928709 Beck DB , et al. (2020)
c.3215T>G p.Phe1072Cys missense_variant Familial Paternal - 31928709 Beck DB , et al. (2020)
c.3226G>A p.Ala1076Thr missense_variant Familial Maternal - 31928709 Beck DB , et al. (2020)
c.3265G>A p.Val1089Met missense_variant Familial Maternal - 31928709 Beck DB , et al. (2020)
c.3028A>G p.Asn1010Asp missense_variant De novo NA Simplex 34719681 Seyama R et al. (2021)
c.1149C>A p.Pro383%3D synonymous_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.1215del p.Trp406GlyfsTer135 frameshift_variant De novo NA - 31928709 Beck DB , et al. (2020)
c.2077C>T p.Gln693Ter stop_gained Familial Paternal Multiplex 34719681 Seyama R et al. (2021)
c.2896T>G p.Cys966Gly missense_variant Familial Maternal Multiplex 34719681 Seyama R et al. (2021)
c.4977_4983del p.His1660ProfsTer52 frameshift_variant Familial Paternal - 31928709 Beck DB , et al. (2020)
c.2722G>T p.Val908Leu missense_variant Familial Both parents Multiplex 30167849 Santos-Cortez RLP , et al. (2018)
Common Variants  

No common variants reported.

SFARI Gene score
S

Syndromic

Score Delta: Score remained at S

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."

Krishnan Probability Score

Score 0.49154532324104

Ranking 5438/25841 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.
ExAC Score

Score 0.9999426505128

Ranking 604/18225 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
Sanders TADA Score

Score 0.94786840619064

Ranking 17451/18665 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).
Zhang D Score

Score 0.25698652035912

Ranking 3379/20870 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.
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