11-32435054-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_024426.6(WT1):c.307G>T(p.Gly103Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000228 in 1,314,318 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. G103G) has been classified as Likely benign.
Frequency
Consequence
NM_024426.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WT1 | NM_024426.6 | c.307G>T | p.Gly103Cys | missense_variant | 1/10 | ENST00000452863.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WT1 | ENST00000452863.10 | c.307G>T | p.Gly103Cys | missense_variant | 1/10 | 1 | NM_024426.6 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000228 AC: 3AN: 1314318Hom.: 0 Cov.: 45 AF XY: 0.00000155 AC XY: 1AN XY: 646974
GnomAD4 genome Cov.: 32
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 | Invitae | May 30, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 98 of the WT1 protein (p.Gly98Cys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 543132). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. - |
Wilms tumor 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Aug 15, 2023 | This missense variant replaces glycine with cysteine at codon 98 of the WT1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with WT1-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at