ClinVar Miner

Submissions for variant NM_012452.3(TNFRSF13B):c.34C>T (p.Arg12Trp)

gnomAD frequency: 0.00006  dbSNP: rs779924436
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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 RCV001871204 SCV002145577 uncertain significance Immunodeficiency, common variable, 2 2025-01-13 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 12 of the TNFRSF13B protein (p.Arg12Trp). This variant is present in population databases (rs779924436, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with TNFRSF13B-related conditions. ClinVar contains an entry for this variant (Variation ID: 1376163). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt TNFRSF13B protein function with a negative predictive value of 95%. 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV002077340 SCV002495992 uncertain significance Immunodeficiency, common variable, 2; Immunoglobulin A deficiency 2 2021-03-30 criteria provided, single submitter clinical testing TNFRSF13B NM_012452.2 exon 1 p.Arg12Trp (c.34C>T): This variant has not been reported in the literature but is present in 0.01% (7/68024) of European alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/17-16972042-G-A?dataset=gnomad_r3). This variant amino acid Tryptophan (Trp) is present in several species including mammals and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Ambry Genetics RCV002552765 SCV003648133 uncertain significance Inborn genetic diseases 2022-09-26 criteria provided, single submitter clinical testing The c.34C>T (p.R12W) alteration is located in exon 1 (coding exon 1) of the TNFRSF13B gene. This alteration results from a C to T substitution at nucleotide position 34, causing the arginine (R) at amino acid position 12 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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