ClinVar Miner

Submissions for variant NM_002439.5(MSH3):c.3136G>A (p.Ala1046Thr)

gnomAD frequency: 0.00005  dbSNP: rs144603433
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001018781 SCV001180057 uncertain significance Hereditary cancer-predisposing syndrome 2023-01-03 criteria provided, single submitter clinical testing The p.A1046T variant (also known as c.3136G>A), located in coding exon 23 of the MSH3 gene, results from a G to A substitution at nucleotide position 3136. The alanine at codon 1046 is replaced by threonine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001048542 SCV001212554 uncertain significance not provided 2023-09-29 criteria provided, single submitter clinical testing An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 822974). This variant has not been reported in the literature in individuals affected with MSH3-related conditions. This variant is present in population databases (rs144603433, gnomAD 0.008%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1046 of the MSH3 protein (p.Ala1046Thr).
Sema4, Sema4 RCV001018781 SCV002536498 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-22 criteria provided, single submitter curation
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001048542 SCV004221095 uncertain significance not provided 2023-08-04 criteria provided, single submitter clinical testing This variant has not been reported in the published literature. The frequency of this variant in the general population, 0.0000071 (2/282572 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.
Baylor Genetics RCV004569972 SCV005054786 uncertain significance Endometrial carcinoma 2023-11-23 criteria provided, single submitter clinical testing
GeneDx RCV001048542 SCV005331813 uncertain significance not provided 2024-02-28 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.