ClinVar Miner

Submissions for variant NM_020937.4(FANCM):c.538A>G (p.Ile180Val)

gnomAD frequency: 0.00012  dbSNP: rs151248588
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000812380 SCV000952691 uncertain significance Fanconi anemia 2024-01-11 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 180 of the FANCM protein (p.Ile180Val). This variant is present in population databases (rs151248588, gnomAD 0.02%). 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: 656065). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". 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.
GeneDx RCV001772099 SCV002002488 uncertain significance not provided 2023-09-28 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Observed in individuals with ovarian cancer (PMID: 28881617); This variant is associated with the following publications: (PMID: 28881617)
Sema4, Sema4 RCV002257979 SCV002529878 uncertain significance Hereditary cancer-predisposing syndrome 2021-06-30 criteria provided, single submitter curation
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001772099 SCV004218820 uncertain significance not provided 2023-03-10 criteria provided, single submitter clinical testing The variant has been reported in individual with breast cancer, ovarian cancer, as well as in unaffected controls (PMIDs: 28881617 (2017) and 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared/genes/ FANCM)). The frequency of this variant in the general population, 0.00022 (29/129136 chromosomes, http://gnomad.broadinstitute.org), is uninformative in 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.

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