ClinVar Miner

Submissions for variant NM_012452.3(TNFRSF13B):c.58C>T (p.Arg20Cys)

gnomAD frequency: 0.00012  dbSNP: rs200013015
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000700484 SCV000829241 uncertain significance Immunodeficiency, common variable, 2 2022-08-23 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 20 of the TNFRSF13B protein (p.Arg20Cys). This variant is present in population databases (rs200013015, gnomAD 0.03%). This missense change has been observed in individual(s) with systemic lupus erythematosus (SLE) and hyper-IgM syndrome or common variable immunodeficiency (PMID: 17464555, 20652909, 33859323, 34441032). ClinVar contains an entry for this variant (Variation ID: 577672). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 Personalized Medicine, Children's Hospital Los Angeles RCV000735375 SCV000854529 uncertain significance Seizure; Micrognathia; Cognitive impairment; Cafe-au-lait spot; Frontal bossing; High forehead; Abnormal basal ganglia morphology; Thoracic scoliosis; Abnormal basal ganglia MRI signal intensity criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001171924 SCV001334827 uncertain significance not provided 2022-08-01 criteria provided, single submitter clinical testing
New York Genome Center RCV001836866 SCV002097834 uncertain significance Immunodeficiency, common variable, 2; Immunoglobulin A deficiency 2 2021-07-23 criteria provided, single submitter clinical testing The inherited heterozygous c.58C>T (p.Arg20Cys) missense variant identified in the TNFRSF13B gene has been reported in a patient affected with hyper-IgM syndrome or common variable immunodeficiency [PMID: 20652909], and in another individual affected with systemic lupus erythematosus (but didn't co-segregate with the disease in that family [PMID: 17464555]. This variant has been reported in ClinVar database as a variant of uncertain significance [Variation ID: 577672]. The variant has 0.0001249 allele frequency in the gnomAD database (19 out of 152,114 heterozygous alleles, no homozygotes) indicating it is not a benign polymorphism in the populations represented in that database. The variant affects a weakly conserved reside and in silico tools provide conflicting interpretations about potential pathogenicity of this variant. Due to the lack of compelling evidence for its pathogenicity, the inherited heterozygous c.58C>T (p.Arg20Cys) missense variant identified in the TNFRSF13B gene of this individual is reported as a variant of uncertain significance.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV004596330 SCV005090288 uncertain significance not specified 2024-07-31 criteria provided, single submitter clinical testing

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