ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.1024G>A (p.Ala342Thr)

gnomAD frequency: 0.00029  dbSNP: rs148028521
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000118863 SCV000153517 uncertain significance not provided 2013-10-17 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000118863 SCV000884918 uncertain significance not provided 2017-05-16 criteria provided, single submitter clinical testing The p.Ala342Thr variant (rs148028521) has been reported in the medical literature in a single individual reported to have autosomal dominant nonsyndromic low-frequency hearing loss (Fukuoka 2007); however, inheritance and specific clinical information were not reported for this individual. The p.Ala342Thr variant is listed in the Genome Aggregation Database (gnomAD) browser with an allele frequency of 0.068% in the South Asian population (identified in 21 out of 30,782 chromosomes; 0 homozygotes), and is classified as a variant of uncertain significance in ClinVar (Variant ID: 130747). The alanine at codon 342 is moderately conserved considering 13 species (Alamut software v2.9.0), and computational analyses predict conflicting effects of this variant on protein structure/function (SIFT: tolerated, PolyPhen2: possibly damaging, MutationTaster: disease causing). Based on the available information, the clinical significance of the p.Ala342Thr variant cannot be determined with certainty.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000825497 SCV000966800 uncertain significance not specified 2018-08-22 criteria provided, single submitter clinical testing The p.Ala342Thr variant in WFS1 has not been previously reported in individuals with hearing loss, Wolfram syndrome, or Wolfram-like syndrome, but has been iden tified in 0.06% (21/30782) of South Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org). This variant has also been reported in ClinVar (Variation ID 130747). Computational prediction tools and co nservation analysis do not provide strong support for or against an impact to th e protein. In summary, the clinical significance of the p.Ala342Thr variant is u ncertain. ACMG/AMP Criteria applied: PM2_Supporting.
Illumina Laboratory Services, Illumina RCV001157249 SCV001318800 uncertain significance Autosomal dominant nonsyndromic hearing loss 6 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina RCV001157250 SCV001318801 uncertain significance WFS1-Related Spectrum Disorders 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV000118863 SCV002374843 likely benign not provided 2024-08-28 criteria provided, single submitter clinical testing
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV002509227 SCV002817337 uncertain risk allele Wolfram syndrome 1 criteria provided, single submitter research 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 rs148028521 in Wolfram's syndrome yet.
Fulgent Genetics, Fulgent Genetics RCV005031615 SCV005660210 uncertain significance Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome 2024-03-05 criteria provided, single submitter clinical testing

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