ClinVar Miner

Submissions for variant NM_006892.4(DNMT3B):c.1139G>A (p.Arg380Gln)

gnomAD frequency: 0.00002  dbSNP: rs148132847
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV002210917 SCV002496097 uncertain significance Immunodeficiency-centromeric instability-facial anomalies syndrome 1 2022-01-27 criteria provided, single submitter clinical testing DNMT3B NM_006892.3 exon 11 p.Arg380Gln (c.1139G>A): This variant has not been reported in the literature but is present in 0.007% (3/41388) of African alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/20-32795421-G-A?dataset=gnomad_r3). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp RCV003089108 SCV003032319 uncertain significance Centromeric instability of chromosomes 1,9 and 16 and immunodeficiency 2023-12-11 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 380 of the DNMT3B protein (p.Arg380Gln). This variant is present in population databases (rs148132847, gnomAD 0.04%). 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: 1675165). 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.

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