ClinVar Miner

Submissions for variant NM_020937.4(FANCM):c.4775C>T (p.Ser1592Leu)

gnomAD frequency: 0.00002  dbSNP: rs759778560
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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 RCV001865032 SCV002126564 uncertain significance Fanconi anemia 2023-07-29 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 1592 of the FANCM protein (p.Ser1592Leu). This variant is present in population databases (rs759778560, gnomAD 0.003%). 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: 1360766). 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 disruptive. 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.
Ambry Genetics RCV003164119 SCV003888524 uncertain significance Inborn genetic diseases 2023-01-31 criteria provided, single submitter clinical testing The c.4775C>T (p.S1592L) alteration is located in exon 19 (coding exon 19) of the FANCM gene. This alteration results from a C to T substitution at nucleotide position 4775, causing the serine (S) at amino acid position 1592 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx RCV003442926 SCV004170144 uncertain significance not provided 2023-04-07 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

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