ClinVar Miner

Submissions for variant NM_006892.4(DNMT3B):c.955A>T (p.Ser319Cys)

dbSNP: rs761984399
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001054118 SCV001218416 uncertain significance Centromeric instability of chromosomes 1,9 and 16 and immunodeficiency 2024-02-24 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 319 of the DNMT3B protein (p.Ser319Cys). This variant is present in population databases (rs761984399, gnomAD 0.0009%). 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: 850034). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt DNMT3B protein function with a negative predictive value of 80%. 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 RCV004977938 SCV005573365 uncertain significance Inborn genetic diseases 2024-11-13 criteria provided, single submitter clinical testing The c.955A>T (p.S319C) alteration is located in exon 9 (coding exon 8) of the DNMT3B gene. This alteration results from a A to T substitution at nucleotide position 955, causing the serine (S) at amino acid position 319 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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