ClinVar Miner

Submissions for variant NM_001042517.2(DIAPH3):c.3283A>G (p.Met1095Val)

gnomAD frequency: 0.00022  dbSNP: rs199814282
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001558414 SCV001780355 likely benign not provided 2020-03-30 criteria provided, single submitter clinical testing 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
Labcorp Genetics (formerly Invitae), Labcorp RCV001558414 SCV002310775 uncertain significance not provided 2021-11-16 criteria provided, single submitter clinical testing This variant is present in population databases (rs199814282, gnomAD 0.06%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1095 of the DIAPH3 protein (p.Met1095Val). This variant has not been reported in the literature in individuals affected with DIAPH3-related conditions. ClinVar contains an entry for this variant (Variation ID: 1195362). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Ambry Genetics RCV004907718 SCV005566403 uncertain significance not specified 2024-08-05 criteria provided, single submitter clinical testing The c.3283A>G (p.M1095V) alteration is located in exon 27 (coding exon 27) of the DIAPH3 gene. This alteration results from a A to G substitution at nucleotide position 3283, causing the methionine (M) at amino acid position 1095 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV003900796 SCV004717892 likely benign DIAPH3-related disorder 2024-01-12 no assertion criteria provided clinical testing 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).

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