ClinVar Miner

Submissions for variant NM_020937.4(FANCM):c.5434C>A (p.Pro1812Thr)

dbSNP: rs3736772
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001042406 SCV001206084 uncertain significance Fanconi anemia 2023-06-28 criteria provided, single submitter clinical testing 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. ClinVar contains an entry for this variant (Variation ID: 840420). This variant has not been reported in the literature in individuals affected with FANCM-related conditions. This variant is present in population databases (rs3736772, gnomAD 0.007%). This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1812 of the FANCM protein (p.Pro1812Thr).
GeneDx RCV001664637 SCV001874834 uncertain significance not provided 2022-04-14 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at a significant frequency in large population cohorts (gnomAD)
Sema4, Sema4 RCV002256651 SCV002529881 uncertain significance Hereditary cancer-predisposing syndrome 2022-01-21 criteria provided, single submitter curation
Genetic Services Laboratory, University of Chicago RCV003151270 SCV003839529 uncertain significance not specified 2022-11-28 no assertion criteria provided clinical testing DNA sequence analysis of the FANCM gene demonstrated a sequence change, c.5434C>A, in exon 21 that results in an amino acid change, p.Pro1812Thr. This sequence change does not appear to have been previously described in individuals with FANCM-related disorders. This sequence change has been described in the gnomAD database with a frequency of 0.007% in the European subpopulation (dbSNP rs3736772). The p.Pro1812Thr change affects a poorly conserved amino acid residue located in a domain of the FANCM protein that is not known to be functional. The p.Pro1812Thr substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Pro1812Thr change remains unknown at this time

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