Human Gene Module / Chromosome 5 / ZSWIM6

ZSWIM6zinc finger SWIM-type containing 6

SFARI Gene Score
S
Syndromic Syndromic
Autism Reports / Total Reports
2 / 6
Rare Variants / Common Variants
6 / 1
Aliases
ZSWIM6, AFND
Associated Syndromes
-
Chromosome Band
5q12.1
Associated Disorders
DD/NDD, ID, ASD, EPS
Relevance to Autism

A recurrent de novo nonsense variant in the ZSWIM6 gene (p.Arg913Ter) was identified in seven unrelated individuals affected with intellectual disability; five of these individuals also met the diagnostic crtieria for autism or autism spectrum disorder (Palmer et al., 2017).

Molecular Function

The protein encoded by this gene contains a zinc finger SWI2/SNF2 and MuDR (SWIM) domain. Proteins with SWIM domains have been found in a diverse number of species and are predicted to interact with DNA or proteins. Mutations in this gene result in acromelic frontonasal dysostosis.

External Links
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Human
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Reports related to ZSWIM6 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary A Recurrent De Novo Nonsense Variant in ZSWIM6 Results in Severe Intellectual Disability without Frontonasal or Limb Malformations Palmer EE , et al. (2017) No ASD
2 Positive Association Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection Pardias AF , et al. (2018) No -
3 Support - Yanagishita T et al. (2021) No DD, ID, epilepsy/seizures
4 Support - Pode-Shakked B et al. (2021) No -
5 Support - Woodbury-Smith M et al. (2022) Yes -
6 Support - Zhou X et al. (2022) Yes -
Rare Variants   (6)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.342C>A p.Phe114Leu missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.2737C>T p.Arg913Ter stop_gained De novo - Simplex 29198722 Palmer EE , et al. (2017)
c.2737C>T p.Arg913Ter stop_gained De novo - Simplex 33958584 Yanagishita T et al. (2021)
c.2737C>T p.Arg913Ter stop_gained De novo - Simplex 34580403 Pode-Shakked B et al. (2021)
c.1566C>T p.Cys522%3D synonymous_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.2737C>T p.Arg913Ter stop_gained Unknown Not maternal Multiplex 29198722 Palmer EE , et al. (2017)
Common Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
T>C - intergenic_variant - - - 29483656 Pardias AF , et al. (2018)
SFARI Gene score
S

Syndromic

A recurrent de novo nonsense variant in the ZSWIM6 gene (p.Arg913Ter) was identified in seven unrelated individuals affected with intellectual disability; five of these individuals also met the diagnostic crtieria for autism or autism spectrum disorder (Palmer et al., 2017).

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."

4/1/2021
S
icon
S

Score remained at S

Description

A recurrent de novo nonsense variant in the ZSWIM6 gene (p.Arg913Ter) was identified in seven unrelated individuals affected with intellectual disability; five of these individuals also met the diagnostic crtieria for autism or autism spectrum disorder (Palmer et al., 2017).

Reports Added
[A recurrent de novo ZSWIM6 variant in a Japanese patient with severe neurodevelopmental delay and frequent vomiting2021]
10/1/2019
S
icon
S

Score remained at S

New Scoring Scheme
Description

A recurrent de novo nonsense variant in the ZSWIM6 gene (p.Arg913Ter) was identified in seven unrelated individuals affected with intellectual disability; five of these individuals also met the diagnostic crtieria for autism or autism spectrum disorder (Palmer et al., 2017).

Reports Added
[New Scoring Scheme]
Krishnan Probability Score

Score 0.4891821456505

Ranking 6559/25841 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 0.33018463385679

Ranking 6342/18225 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 0.94460516641272

Ranking 16141/18665 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 0.19737481868636

Ranking 4304/20870 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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