Human Gene Module / Chromosome 19 / SCAF1

SCAF1SR-related CTD associated factor 1

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
4 / 4
Rare Variants / Common Variants
26 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
19q13.33
Associated Disorders
-
Relevance to Autism

A two-stage analysis of rare de novo and inherited coding variants in 42,607 ASD cases, including 35,130 new cases from the SPARK cohort, in Zhou et al., 2022 identified SCAF1 as a gene reaching exome-wide significance (P < 2.5E-06); association of SCAF1 with ASD risk was driven by both de novo variants and rare loss-of-function variants. Wilfert et al., 2021 identified two ultra-rare inherited frameshift variants in SCAF1 that were exclusively transmitted to ASD probands from two independent families.

Molecular Function

Enables RNA polymerase II C-terminal domain binding activity. Predicted to be involved in RNA splicing; mRNA processing; and transcription by RNA polymerase II. Predicted to be located in nucleus.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
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SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to SCAF1 (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism Satterstrom FK et al. (2020) Yes -
2 Support - Wilfert AB et al. (2021) Yes -
3 Primary - Zhou X et al. (2022) Yes -
4 Support - Wang J et al. (2023) Yes -
Rare Variants   (26)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.874C>T p.Gln292Ter stop_gained Unknown - - 35982159 Zhou X et al. (2022)
c.3717C>G p.Tyr1239Ter stop_gained Unknown - - 35982159 Zhou X et al. (2022)
c.2969C>T p.Pro990Leu missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.166+1G>A - splice_site_variant Familial - Multiplex 35982159 Zhou X et al. (2022)
c.2185G>T p.Glu729Ter stop_gained De novo - - 31981491 Satterstrom FK et al. (2020)
c.3361C>T p.Arg1121Ter splice_site_variant De novo - - 35982159 Zhou X et al. (2022)
c.2282C>T p.Ser761Phe missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.2516T>C p.Val839Ala missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.2995T>A p.Cys999Ser missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.2003C>T p.Pro668Leu missense_variant De novo - Simplex 37393044 Wang J et al. (2023)
c.3817C>T p.Arg1273Cys missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.2301del p.Ser768LeufsTer64 frameshift_variant Unknown - - 35982159 Zhou X et al. (2022)
c.3052del p.Arg1018GlufsTer89 frameshift_variant Unknown - - 35982159 Zhou X et al. (2022)
c.3139dup p.Ala1047GlyfsTer21 frameshift_variant Unknown - - 35982159 Zhou X et al. (2022)
c.240_241del p.Gly82HisfsTer2 frameshift_variant Unknown - - 35982159 Zhou X et al. (2022)
c.3571_3572del p.Lys1191GlufsTer8 frameshift_variant Unknown - - 35982159 Zhou X et al. (2022)
c.1496_1511dup p.Pro505LeufsTer153 frameshift_variant Unknown - - 35982159 Zhou X et al. (2022)
c.1196del p.Pro399ArgfsTer65 frameshift_variant Familial Paternal - 35982159 Zhou X et al. (2022)
c.1787dup p.Ser597GlnfsTer56 frameshift_variant Familial Maternal - 35982159 Zhou X et al. (2022)
c.3540dup p.Thr1181HisfsTer10 frameshift_variant Familial - Multiplex 35982159 Zhou X et al. (2022)
c.1787dup p.Ser597GlnfsTer56 frameshift_variant Familial - Simplex 34312540 Wilfert AB et al. (2021)
c.2966del p.Thr989IlefsTer118 frameshift_variant Unknown Not maternal - 35982159 Zhou X et al. (2022)
c.3540dup p.Thr1181HisfsTer10 frameshift_variant Unknown Not maternal - 35982159 Zhou X et al. (2022)
c.2863_2866del p.Gly955ProfsTer151 frameshift_variant Familial Maternal - 35982159 Zhou X et al. (2022)
c.1234_1256del p.Pro412TyrfsTer233 frameshift_variant Unknown Not maternal - 35982159 Zhou X et al. (2022)
c.2863_2866del p.Gly955ProfsTer151 frameshift_variant Familial - Simplex 34312540 Wilfert AB et al. (2021)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

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.

10/1/2022
icon
2

Increased from to 2

Krishnan Probability Score

Score 0.4815566187181

Ranking 7923/25841 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 0.99878753876853

Ranking 1111/18225 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 0.94383343080014

Ranking 15840/18665 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 0.18077107172565

Ranking 4586/20870 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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