ClinVar Miner

Submissions for variant NM_020937.4(FANCM):c.4959G>A (p.Met1653Ile)

gnomAD frequency: 0.00014  dbSNP: rs143152888
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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 RCV000693498 SCV000821369 uncertain significance Fanconi anemia 2023-09-11 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1653 of the FANCM protein (p.Met1653Ile). This variant is present in population databases (rs143152888, gnomAD 0.04%). 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: 572179). 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 isoleucine 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 RCV001562968 SCV001785824 uncertain significance not provided 2022-10-20 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
Fulgent Genetics, Fulgent Genetics RCV002493185 SCV002800797 uncertain significance Spermatogenic failure 28; Premature ovarian failure 15 2022-05-22 criteria provided, single submitter clinical testing
Ambry Genetics RCV004619388 SCV005113463 uncertain significance Inborn genetic diseases 2024-05-14 criteria provided, single submitter clinical testing The c.4959G>A (p.M1653I) alteration is located in exon 20 (coding exon 20) of the FANCM gene. This alteration results from a G to A substitution at nucleotide position 4959, causing the methionine (M) at amino acid position 1653 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Mendelics RCV004702332 SCV005205572 likely benign Hereditary cancer 2024-09-11 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following: it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease, and/or has normal protein function, and/or has lack of segregation with disease, and/or has been detected in co-occurrence with known pathogenic variant, and/or has lack of disease association in case-control studies, and/or is located in a region inconsistent with a known cause of pathogenicity.

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