rs121907909
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_024426.6(WT1):c.1387C>T(p.Arg463Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000658 in 151,896 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. R463R) has been classified as Likely benign.
Frequency
Consequence
NM_024426.6 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WT1 | NM_024426.6 | c.1387C>T | p.Arg463Ter | stop_gained | 9/10 | ENST00000452863.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WT1 | ENST00000452863.10 | c.1387C>T | p.Arg463Ter | stop_gained | 9/10 | 1 | NM_024426.6 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151896Hom.: 0 Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 151896Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74178
ClinVar
Submissions by phenotype
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 01, 2020 | This variant is expected to result in the loss of a functional protein. This variant was not reported in large, multi-ethnic, general populations (http://gnomad.broadinstitute.org). This variant appears to occur de novo in multiple individuals with clinical features associated with this gene. - |
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Nov 15, 2019 | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek 2016); This variant is associated with the following publications: (PMID: 15150775, 23117548, 12471221, 27701157, 8388765, 1317572, 21508141, 23515051, 19205749, 21851196, 9108089, 25818337, 10571943, 29869118, 30712057, 31278746) - |
11p partial monosomy syndrome;C0950121:Drash syndrome;C0950122:Frasier syndrome;CN033288:Wilms tumor 1 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Sep 13, 2023 | This variant is also known as p.Arg390*. This sequence change creates a premature translational stop signal (p.Arg458*) in the WT1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in WT1 are known to be pathogenic (PMID: 15150775). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with Wilms tumor and Denys-Drash syndrome (PMID: 9108089, 10571943, 12471221, 15150775, 21508141, 21851196, 23117548, 23515051). ClinVar contains an entry for this variant (Variation ID: 3494). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. - |
11p partial monosomy syndrome;C0344542:Aniridia 1;C0345967:Mesothelioma, malignant;C0950121:Drash syndrome;C0950122:Frasier syndrome;C1837026:Meacham syndrome;C3151568:Nephrotic syndrome, type 4;CN033288:Wilms tumor 1 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 24, 2021 | - - |
Frasier syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 01, 1999 | - - |
Focal segmental glomerulosclerosis Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Feb 24, 2022 | - - |
Wilms tumor 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 15, 1997 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at