ClinVar Miner

Submissions for variant NM_001080476.3(GRXCR1):c.469G>T (p.Glu157Ter)

gnomAD frequency: 0.00001  dbSNP: rs774844858
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001269174 SCV001448458 likely pathogenic Autosomal recessive nonsyndromic hearing loss 25 2020-11-18 criteria provided, single submitter clinical testing Variant summary: GRXCR1 c.469G>T (p.Glu157X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 4.4e-05 in 249152 control chromosomes. To our knowledge, no occurrence of c.469G>T in individuals affected with Deafness, Autosomal Recessive 25 and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Baylor Genetics RCV001269174 SCV001525176 pathogenic Autosomal recessive nonsyndromic hearing loss 25 2019-01-21 criteria provided, single submitter clinical testing This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Invitae RCV001880175 SCV002186055 pathogenic not provided 2022-08-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu157*) in the GRXCR1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GRXCR1 are known to be pathogenic (PMID: 20137778, 26226137, 26969326). This variant is present in population databases (rs774844858, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with GRXCR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 987829). For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics, part of Exact Sciences RCV003416141 SCV004117625 likely pathogenic GRXCR1-related disorder 2022-12-20 criteria provided, single submitter clinical testing The GRXCR1 c.469G>T variant is predicted to result in premature protein termination (p.Glu157*). To our knowledge, this variant has not been reported in the literature. Other protein truncating variants in this gene have been reported in homozygous or compound heterozygous state in individuals affected with deafness (Bademci et al 2015. PubMed ID: 26226137; Sloan-Heggen et a 2016. PubMed ID: 26969326; Schraders et al. 2010. PubMed ID: 20137778). This variant is reported in 0.032% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/4-42964993-G-T). Nonsense variants in GRXCR1 are expected to be pathogenic. This variant is interpreted as likely pathogenic.

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