ClinVar Miner

Submissions for variant NM_006892.4(DNMT3B):c.167C>T (p.Ser56Phe)

gnomAD frequency: 0.00004  dbSNP: rs764811687
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000522310 SCV000621396 uncertain significance not provided 2017-10-10 criteria provided, single submitter clinical testing The S56F variant in the DNMT3B gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The S56F variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The S56F variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret S56F as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV002231639 SCV000827182 uncertain significance Centromeric instability of chromosomes 1,9 and 16 and immunodeficiency 2022-07-05 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 56 of the DNMT3B protein (p.Ser56Phe). This variant is present in population databases (rs764811687, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with DNMT3B-related conditions. ClinVar contains an entry for this variant (Variation ID: 452578). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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.

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