rs71524349
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_006005.3(WFS1):āc.353A>Cā(p.Asp118Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000494 in 1,608,038 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D118E) has been classified as Uncertain significance.
Frequency
Consequence
NM_006005.3 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 |
---|---|---|---|---|---|---|---|
WFS1 | NM_006005.3 | c.353A>C | p.Asp118Ala | missense_variant | 4/8 | ENST00000226760.5 | |
WFS1 | NM_001145853.1 | c.353A>C | p.Asp118Ala | missense_variant | 4/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WFS1 | ENST00000226760.5 | c.353A>C | p.Asp118Ala | missense_variant | 4/8 | 1 | NM_006005.3 | P2 |
Frequencies
GnomAD3 genomes AF: 0.00256 AC: 389AN: 152188Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000631 AC: 149AN: 236166Hom.: 0 AF XY: 0.000524 AC XY: 67AN XY: 127808
GnomAD4 exome AF: 0.000278 AC: 405AN: 1455732Hom.: 0 Cov.: 32 AF XY: 0.000234 AC XY: 169AN XY: 723314
GnomAD4 genome AF: 0.00255 AC: 389AN: 152306Hom.: 0 Cov.: 33 AF XY: 0.00220 AC XY: 164AN XY: 74474
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:5
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 07, 2021 | This variant is associated with the following publications: (PMID: 26435059, 27068579) - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2019 | - - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Aug 05, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | May 26, 2018 | The WFS1 c.353A>C; p.Asp118Ala variant (rs71524349), is reported in the literature in an individual with prelingual nonsyndromic hearing loss (Sommen 2016); however, inheritance and specific clinical information were not reported for this individual. This variant has also been observed in our laboratory in the homozygous state in an individual who had an alternate molecular basis for disease. This variant is found in the African population with an allele frequency of 0.90% (203/22,568 alleles) in the Genome Aggregation Database and is reported as benign/likely benign in ClinVar (Variation ID: 178584). Based on the available information, this variant is classified as likely benign. - |
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 26, 2014 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 30, 2012 | Asp118Ala in Exon 04 of WFS1: This variant is not expected to have clinical sign ificance because it has been identified in 0.8% (28/3732) of African American ch romosomes from a broad population by the NHLBI Exome Sequencing Project (http:// evs.gs.washington.edu/EVS; dbSNP rs71524349). - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Monogenic diabetes Benign:1
Benign, criteria provided, single submitter | research | Personalized Diabetes Medicine Program, University of Maryland School of Medicine | Sep 07, 2018 | ACMG criteria: PP3 (REVEL 0.801 + 10 predictors), BA1(0.9% MAF in gnomAD Africans when prevalence of Wolfram is 1:500000 which leads to carrier frequency of ~1:350/0.3%)=Benign - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at