ClinVar Miner

Submissions for variant NM_020937.4(FANCM):c.3221T>C (p.Ile1074Thr)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002728426 SCV003562037 uncertain significance Inborn genetic diseases 2021-07-06 criteria provided, single submitter clinical testing The c.3221T>C (p.I1074T) alteration is located in exon 14 (coding exon 14) of the FANCM gene. This alteration results from a T to C substitution at nucleotide position 3221, causing the isoleucine (I) at amino acid position 1074 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003523140 SCV004284231 uncertain significance Fanconi anemia 2023-10-27 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1074 of the FANCM protein (p.Ile1074Thr). This variant is not present in population databases (gnomAD no frequency). 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: 2234951). 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 threonine 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 RCV004725585 SCV005332992 uncertain significance not provided 2023-11-09 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

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