ClinVar Miner

Submissions for variant NM_020937.4(FANCM):c.232T>C (p.Ser78Pro)

gnomAD frequency: 0.00004  dbSNP: rs995677452
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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 RCV001984384 SCV002280458 uncertain significance Fanconi anemia 2021-09-24 criteria provided, single submitter clinical testing This sequence change replaces serine with proline at codon 78 of the FANCM protein (p.Ser78Pro). The serine residue is weakly conserved and there is a moderate physicochemical difference between serine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with FANCM-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 RCV002511123 SCV002820805 uncertain significance not provided 2022-07-12 criteria provided, single submitter clinical testing 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
Ambry Genetics RCV002625341 SCV003648572 uncertain significance Inborn genetic diseases 2022-09-22 criteria provided, single submitter clinical testing The c.232T>C (p.S78P) alteration is located in exon 1 (coding exon 1) of the FANCM gene. This alteration results from a T to C substitution at nucleotide position 232, causing the serine (S) at amino acid position 78 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV004529079 SCV004107154 uncertain significance FANCM-related disorder 2023-06-20 criteria provided, single submitter clinical testing The FANCM c.232T>C variant is predicted to result in the amino acid substitution p.Ser78Pro. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.023% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/14-45605466-T-C) and is reported in ClinVar as uncertain (https://www.ncbi.nlm.nih.gov/clinvar/variation/1493455/). 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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