chr11-32435333-C-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBS2_Supporting
The ENST00000452863.10(WT1):c.28G>T(p.Ala10Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000588 in 1,531,432 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A10D) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000452863.10 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
WT1 | NM_024426.6 | c.28G>T | p.Ala10Ser | missense_variant | 1/10 | ENST00000452863.10 | NP_077744.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
WT1 | ENST00000452863.10 | c.28G>T | p.Ala10Ser | missense_variant | 1/10 | 1 | NM_024426.6 | ENSP00000415516 |
Frequencies
GnomAD3 genomes AF: 0.0000331 AC: 5AN: 151042Hom.: 1 Cov.: 30
GnomAD4 exome AF: 0.00000290 AC: 4AN: 1380390Hom.: 0 Cov.: 44 AF XY: 0.00000147 AC XY: 1AN XY: 681014
GnomAD4 genome AF: 0.0000331 AC: 5AN: 151042Hom.: 1 Cov.: 30 AF XY: 0.0000271 AC XY: 2AN XY: 73718
ClinVar
Submissions by phenotype
11p partial monosomy syndrome;C0950121:Drash syndrome;C0950122:Frasier syndrome;CN033288:Wilms tumor 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 25, 2023 | This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 5 of the WT1 protein (p.Ala5Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with WT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 802670). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Drash syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
WT1-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 27, 2023 | The WT1 c.13G>T variant is predicted to result in the amino acid substitution p.Ala5Ser. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare, and is interpreted as a variant of uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/802670/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | Apr 28, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at