ClinVar Miner

Submissions for variant NM_052945.3(TNFRSF13C):c.475C>T (p.His159Tyr) (rs61756766)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000658943 SCV000605404 uncertain significance not provided 2017-09-29 criteria provided, single submitter clinical testing In vitro functional studies with p.His159Tyr showed that signaling through this variant results in increased immunoglobulin production compared with the wild-type (Hildebrand 2010). The p.His159Tyr variant was reported in patients with non-Hodgkin lymphomas (Hildebrand 2010). The p.His159Tyr variant was also reported in a patient with CVID with severe phenotype of recurrent sinopulmonary infections, chronic sinusitis, bronchiectasis, hepatosplenomegaly, chronic diarrhea, osteoporosis and sero-negative spondylarthropathy who also carried the Pro21Arg variant (Kutukculer 2012). Seven patients with hypogammaglobulinemia were also identified to carry both Pro21Arg and His159Tyr variants (Mouillot 2010). Additionally, a patient with Good’s syndrome carried these two variants (Lougaris 2014). Moreover, the p.His159Tyr variant was found in another patient with CVID but also in her asymptomatic father and one control (Losi 2005). The His159Tyr variant was also reported in patients with Sjögren's syndrome as well as in healthy controls (Papageorgiou 2015). This variant was found in one percent of studied controls in New Zealand (Koopmans 2012). His159Tyr is listed in the genome aggregation database Browser with overall allele frequency of 0.6 percent, including 9 homozygotes. Hammarstom (2008) reported no association of Pro21Arg and His159Tyr variants with CVID. Most recently, Lougaris (2016) and colleagues described a family with CVID with a monoallelic (i.e. on the same chromosome) configuration of the Pro21Arg and His159Tyr variants in the TNFRSF13C (BAFF-R) gene. Based on current understanding, the role of the His159Tyr variant alone or in combination with Pro21Arg in CVID remains uncertain.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000658943 SCV000780745 likely benign not provided 2018-09-30 criteria provided, single submitter clinical testing
Invitae RCV000648327 SCV000770143 likely benign Common variable immunodeficiency 4 2017-11-28 criteria provided, single submitter clinical testing

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