ClinVar Miner

Submissions for variant NM_006892.4(DNMT3B):c.1807G>A (p.Ala603Thr)

gnomAD frequency: 0.00001  dbSNP: rs121908943
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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 RCV002512866 SCV003443369 likely pathogenic Centromeric instability of chromosomes 1,9 and 16 and immunodeficiency 2023-03-18 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 603 of the DNMT3B protein (p.Ala603Thr). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this missense change affects DNMT3B function (PMID: 15580563, 16501171). 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 expected to disrupt DNMT3B protein function. ClinVar contains an entry for this variant (Variation ID: 6740). This missense change has been observed in individual(s) with immunodeficiency, centromeric instability, and facial anomalies syndrome (PMID: 10588719, 28713390; Invitae). This variant is present in population databases (rs121908943, gnomAD 0.003%).
OMIM RCV000007132 SCV000027328 pathogenic Immunodeficiency-centromeric instability-facial anomalies syndrome 1 1999-10-29 no assertion criteria provided literature only

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