ClinVar Miner

Submissions for variant NM_020937.4(FANCM):c.242C>T (p.Ala81Val)

gnomAD frequency: 0.00002  dbSNP: rs538464580
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001053782 SCV001218060 uncertain significance Fanconi anemia 2025-01-20 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 81 of the FANCM protein (p.Ala81Val). This variant is present in population databases (rs538464580, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with FANCM-related conditions. ClinVar contains an entry for this variant (Variation ID: 849752). 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.
GeneDx RCV001786429 SCV002028686 uncertain significance not provided 2024-09-27 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001786429 SCV005626263 uncertain significance not provided 2024-06-25 criteria provided, single submitter clinical testing The FANCM c.242C>T (p.Ala81Val) variant has been reported in the published literature in individuals with breast cancer and reportedly healthy individuals (PMID: 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared/genes/FANCM)). The frequency of this variant in the general population, 0.0013 (40/30616 chromosomes in South Asian subpopulation (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is higher than would generally be expected for pathogenic variants in this gene. 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.
Fulgent Genetics, Fulgent Genetics RCV005005009 SCV005629794 uncertain significance Spermatogenic failure 28; Premature ovarian failure 15 2024-05-14 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004738137 SCV005352871 likely benign FANCM-related disorder 2024-09-28 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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