ClinVar Miner

Submissions for variant NM_020937.4(FANCM):c.3658A>T (p.Ile1220Phe)

gnomAD frequency: 0.00001  dbSNP: rs201839320
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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 RCV000813255 SCV000953606 uncertain significance Fanconi anemia 2025-01-12 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 1220 of the FANCM protein (p.Ile1220Phe). This variant is present in population databases (rs201839320, gnomAD 0.007%). 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: 656759). 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 RCV002245684 SCV002513005 uncertain significance not provided 2021-11-02 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); 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 RCV002487776 SCV002790652 uncertain significance Spermatogenic failure 28; Premature ovarian failure 15 2024-06-04 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004738020 SCV005343150 uncertain significance FANCM-related disorder 2024-03-20 no assertion criteria provided clinical testing The FANCM c.3658A>T variant is predicted to result in the amino acid substitution p.Ile1220Phe. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0070% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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