rs916583720
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBS2_Supporting
The NM_024426.6(WT1):c.343C>T(p.Pro115Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000162 in 1,485,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. P115H) has been classified as Uncertain significance.
Frequency
Consequence
NM_024426.6 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 | UniProt |
---|---|---|---|---|---|---|---|
WT1 | NM_024426.6 | c.343C>T | p.Pro115Ser | missense_variant | 1/10 | ENST00000452863.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WT1 | ENST00000452863.10 | c.343C>T | p.Pro115Ser | missense_variant | 1/10 | 1 | NM_024426.6 |
Frequencies
GnomAD3 genomes ? AF: 0.0000921 AC: 14AN: 151966Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000241 AC: 2AN: 83158Hom.: 0 AF XY: 0.0000217 AC XY: 1AN XY: 46150
GnomAD4 exome AF: 0.00000750 AC: 10AN: 1333364Hom.: 0 Cov.: 45 AF XY: 0.00000457 AC XY: 3AN XY: 656396
GnomAD4 genome ? AF: 0.0000921 AC: 14AN: 151966Hom.: 0 Cov.: 32 AF XY: 0.0000943 AC XY: 7AN XY: 74222
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 | Jan 28, 2024 | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 110 of the WT1 protein (p.Pro110Ser). 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: 406698). 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 | Baylor Genetics | Feb 13, 2024 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 03, 2022 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 8486616) - |
Wilms tumor 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Nov 20, 2023 | This variant is located in 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 been identified in 5/114288 chromosomes 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