Human Gene Module / Chromosome 6 / ZNF292

ZNF292zinc finger protein 292

Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
4 / 5
Rare Variants / Common Variants
27 / 0
Aliases
ZNF292, Nbla00365,  ZFP292,  ZN-16,  Zn-15,  bA393I2.3
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation, Syndromic
Chromosome Band
6q14.3
Associated Disorders
ADHD
Relevance to Autism

A de novo loss-of-function (LoF) variant in the ZNF292 gene was identified in a female ASD proband with positive family history from the Autism Sequencing Consortium (Neale et al., 2012); a second de novo LoF variant in this gene was identified in an ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort (Wang et al., 2016).

Molecular Function

The protein encoded by this gene may be involved in transcriptional regulation.

Reports related to ZNF292 (5 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Patterns and rates of exonic de novo mutations in autism spectrum disorders. Neale BM , et al. (2012) Yes -
2 Support De novo genic mutations among a Chinese autism spectrum disorder cohort. Wang T , et al. (2016) Yes -
3 Support Exome Pool-Seq in neurodevelopmental disorders. Popp B , et al. (2017) No -
4 Support Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model. Guo H , et al. (2018) Yes -
5 Recent Recommendation De novo and inherited variants in ZNF292 underlie a neurodevelopmental disorder with features of autism spectrum disorder. Mirzaa GM , et al. (2019) Yes ADHD
Rare Variants   (27)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.265C>T p.Arg89Ter stop_gained De novo NA Simplex 31723249 Mirzaa GM , et al. (2019)
c.1360C>T p.Arg454Ter stop_gained De novo NA Simplex 31723249 Mirzaa GM , et al. (2019)
c.1567C>T p.Gln523Ter stop_gained De novo NA Simplex 31723249 Mirzaa GM , et al. (2019)
c.3812C>A p.Ser1271Ter stop_gained De novo NA Simplex 31723249 Mirzaa GM , et al. (2019)
c.4897A>T p.Lys1633Ter stop_gained De novo NA Simplex 31723249 Mirzaa GM , et al. (2019)
c.5185C>T p.Gln1729Ter stop_gained De novo NA Simplex 31723249 Mirzaa GM , et al. (2019)
c.6343C>T p.Arg2115Ter stop_gained De novo NA Simplex 31723249 Mirzaa GM , et al. (2019)
c.6541C>T p.Arg2181Ter stop_gained De novo NA Simplex 31723249 Mirzaa GM , et al. (2019)
c.3709dup p.Thr1237AsnfsTer20 frameshift_variant De novo NA - 31723249 Mirzaa GM , et al. (2019)
c.2490_2494dup p.Ser832IlefsTer28 frameshift_variant De novo NA - 27824329 Wang T , et al. (2016)
c.4417dup p.Ser1473PhefsTer5 frameshift_variant De novo NA Simplex 30564305 Guo H , et al. (2018)
c.3066_3069del p.Ser1023GlnfsTer33 frameshift_variant De novo NA - 29158550 Popp B , et al. (2017)
c.5288A>G p.Lys1763Arg missense_variant Familial Maternal Multiplex 30564305 Guo H , et al. (2018)
c.2814_2821dup p.Val941AlafsTer68 frameshift_variant De novo NA - 31723249 Mirzaa GM , et al. (2019)
c.433del p.Ser145AlafsTer7 frameshift_variant De novo NA Simplex 31723249 Mirzaa GM , et al. (2019)
c.6661_6664del p.Leu2221SerfsTer10 frameshift_variant De novo NA - 31723249 Mirzaa GM , et al. (2019)
c.2170del p.Cys724AlafsTer9 frameshift_variant De novo NA Simplex 31723249 Mirzaa GM , et al. (2019)
c.6279dup p.Arg2094ThrfsTer10 frameshift_variant De novo NA Simplex 31723249 Mirzaa GM , et al. (2019)
c.1160del p.Arg387LeufsTer5 frameshift_variant De novo NA Multiplex 31723249 Mirzaa GM , et al. (2019)
c.3066_3069del p.Glu1022AspfsTer3 frameshift_variant De novo NA Simplex 31723249 Mirzaa GM , et al. (2019)
c.3460_3463del p.Val1154IlefsTer7 frameshift_variant De novo NA Simplex 31723249 Mirzaa GM , et al. (2019)
c.5515_5569del p.Glu1839HisfsTer6 frameshift_variant De novo NA Simplex 31723249 Mirzaa GM , et al. (2019)
c.5959_5965dup p.Gly1989AlafsTer9 frameshift_variant De novo NA Simplex 31723249 Mirzaa GM , et al. (2019)
c.6142_6145del p.Lys2048ValfsTer11 frameshift_variant De novo NA Simplex 31723249 Mirzaa GM , et al. (2019)
c.6160_6161del p.Glu2054LysfsTer14 frameshift_variant De novo NA Simplex 31723249 Mirzaa GM , et al. (2019)
c.3724del p.Gln1242LysfsTer5 frameshift_variant Familial Maternal Simplex 31723249 Mirzaa GM , et al. (2019)
c.265C>T p.Arg89Ter stop_gained De novo NA Not simplex (positive family history) 22495311 Neale BM , et al. (2012)
Common Variants  

No common variants reported.

SFARI Gene score
1

High Confidence

A de novo loss-of-function (LoF) variant in the ZNF292 gene was identified in a female ASD proband with positive family history from the Autism Sequencing Consortium (Neale et al., 2012); a second de novo LoF variant in this gene was identified in an ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort (Wang et al., 2016). Mirzaa et al., 2019 described a cohort of 28 individuals with putatively pathogenic ZNF292 variants that presented with a neurodevelopmental disorder characterized by developmental delay/intellectual disability (96%), speech delay (93%), and ASD or autistic features (61%); ADHD, tone abnormalities, structural brain abnormalities, dysmorphic features, ocular features, and growth failure were also observed in at least 30% of affected individuals.

Score Delta: Score remained at 4S

1

High Confidence

See all Category 1 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.

10/1/2019
4
icon
3S

Decreased from 4 to 3S

New Scoring Scheme
Description

A de novo loss-of-function (LoF) variant in the ZNF292 gene was identified in a female ASD proband with positive family history from the Autism Sequencing Consortium (Neale et al., 2012); a second de novo LoF variant in this gene was identified in an ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort (Wang et al., 2016). Mirzaa et al., 2019 described a cohort of 28 individuals with putatively pathogenic ZNF292 variants that presented with a neurodevelopmental disorder characterized by developmental delay/intellectual disability (96%), speech delay (93%), and ASD or autistic features (61%); ADHD, tone abnormalities, structural brain abnormalities, dysmorphic features, ocular features, and growth failure were also observed in at least 30% of affected individuals.

1/1/2019
4
icon
4

Decreased from 4 to 4

Description

A de novo loss-of-function (LoF) variant in the ZNF292 gene was identified in a female ASD proband with positive family history from the Autism Sequencing Consortium (Neale et al., 2012); a second de novo LoF variant in this gene was identified in an ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort (Wang et al., 2016).

10/1/2017
4
icon
4

Decreased from 4 to 4

Description

A de novo loss-of-function (LoF) variant in the ZNF292 gene was identified in a female ASD proband with positive family history from the Autism Sequencing Consortium (Neale et al., 2012); a second de novo LoF variant in this gene was identified in an ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort (Wang et al., 2016).

10/1/2016
icon
4

Increased from to 4

Description

A de novo loss-of-function (LoF) variant in the ZNF292 gene was identified in a female ASD proband with positive family history from the Autism Sequencing Consortium (Neale et al., 2012); a second de novo LoF variant in this gene was identified in an ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort (Wang et al., 2016).

Krishnan Probability Score

Score 0.57067867734506

Ranking 885/25841 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 0.99997698413608

Ranking 524/18225 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
Iossifov Probability Score

Score 0.969

Ranking 60/239 scored genes


[Show Scoring Methodology]
Supplementary dataset S2 in the paper by Iossifov et al. (PNAS 112, E5600-E5607 (2015)) lists 239 genes with a probability of at least 0.8 of being associated with autism risk (column I). This probability metric combines the evidence from de novo likely-gene- disrupting and missense mutations and assesses it against the background mutation rate in unaffected individuals from the University of Washington’s Exome Variant Sequence database (evs.gs.washington.edu/EVS/). The list of probability scores can be found here: www.pnas.org/lookup/suppl/doi:10.1073/pnas.1516376112/- /DCSupplemental/pnas.1516376112.sd02.xlsx
Sanders TADA Score

Score 0.67146936298208

Ranking 996/18665 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 0.64062888495895

Ranking 24/20870 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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SFARI Gene Update

We are pleased to announce some changes to the ongoing curation of the data in SFARI Gene. In the context of a continued effort to develop the human gene module and its manually curated list of autism risk genes, we are modifying other aspects of the site to focus on the information that is of greatest interest to the research community. The version of SFARI Gene that has been developed until now will be frozen and will remain available as “SFARI Gene Archive”. Please see the announcement for more details.
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