ClinVar Miner

Submissions for variant NM_020937.4(FANCM):c.1353G>T (p.Lys451Asn)

gnomAD frequency: 0.00001  dbSNP: rs771239660
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001341954 SCV001535851 uncertain significance Fanconi anemia 2024-10-15 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 451 of the FANCM protein (p.Lys451Asn). This variant is present in population databases (rs771239660, 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: 1038623). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 RCV002511080 SCV002820813 uncertain significance not provided 2022-07-15 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); 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; In-silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.
Ambry Genetics RCV004978364 SCV005586958 uncertain significance Inborn genetic diseases 2024-11-30 criteria provided, single submitter clinical testing The p.K451N variant (also known as c.1353G>T), located in coding exon 8 of the FANCM gene, results from a G to T substitution at nucleotide position 1353. The lysine at codon 451 is replaced by asparagine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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