ClinVar Miner

Submissions for variant NM_020937.4(FANCM):c.1255A>G (p.Met419Val)

gnomAD frequency: 0.00002  dbSNP: rs552281088
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002026492 SCV002301505 uncertain significance Fanconi anemia 2021-07-14 criteria provided, single submitter clinical testing This variant is present in population databases (rs552281088, ExAC 0.01%). 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. 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. This variant has not been reported in the literature in individuals affected with FANCM-related conditions. This sequence change replaces methionine with valine at codon 419 of the FANCM protein (p.Met419Val). The methionine residue is weakly conserved and there is a small physicochemical difference between methionine and valine.
GeneDx RCV003328692 SCV004035584 uncertain significance not provided 2023-09-12 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); 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
Fulgent Genetics, Fulgent Genetics RCV005002774 SCV005629811 uncertain significance Spermatogenic failure 28; Premature ovarian failure 15 2024-06-12 criteria provided, single submitter clinical testing
Ambry Genetics RCV005343269 SCV006002389 uncertain significance Inborn genetic diseases 2024-12-15 criteria provided, single submitter clinical testing The p.M419V variant (also known as c.1255A>G), located in coding exon 7 of the FANCM gene, results from an A to G substitution at nucleotide position 1255. The methionine at codon 419 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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