rs150894674
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 4P and 12B. PM1PM2BP4_StrongBP6_Very_Strong
The NM_006005.3(WFS1):c.1321G>A(p.Val441Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000161 in 1,613,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_006005.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WFS1 | NM_006005.3 | c.1321G>A | p.Val441Met | missense_variant | 8/8 | ENST00000226760.5 | |
WFS1 | NM_001145853.1 | c.1321G>A | p.Val441Met | missense_variant | 8/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WFS1 | ENST00000226760.5 | c.1321G>A | p.Val441Met | missense_variant | 8/8 | 1 | NM_006005.3 | P2 | |
ENST00000661896.1 | n.1337+2799C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.000881 AC: 134AN: 152076Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000263 AC: 66AN: 250864Hom.: 0 AF XY: 0.000221 AC XY: 30AN XY: 135614
GnomAD4 exome AF: 0.0000876 AC: 128AN: 1461362Hom.: 0 Cov.: 103 AF XY: 0.0000770 AC XY: 56AN XY: 726996
GnomAD4 genome AF: 0.000867 AC: 132AN: 152194Hom.: 0 Cov.: 33 AF XY: 0.000847 AC XY: 63AN XY: 74410
ClinVar
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 18, 2020 | This variant is associated with the following publications: (PMID: 11244483) - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 30, 2012 | Val441Met in Exon 08 of WFS1: This variant is not expected to have clinical sign ificance because it has been identified in 0.4% (14/3738) of African American ch romosomes from a broad population by the NHLBI Exome Sequencing Project (http:// evs.gs.washington.edu/EVS; dbSNP rs150894674). - |
WFS1-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 01, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Wolfram syndrome 1 Benign:1
Likely benign, criteria provided, single submitter | research | Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic | - | Potent mutations in WFS1 gene are associated with Wolfram's syndrome, an autosomal recessive condition, which cause diabetes mellitus, diabetes insipidus, deafness and optic atrophy. However no sufficient evidence is found to ascertain the role of this particular variant rs150894674 in Wolfram's syndrome yet. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at