ClinVar Miner

Submissions for variant NM_001167.4(XIAP):c.1408A>T (p.Thr470Ser)

gnomAD frequency: 0.00050  dbSNP: rs143165174
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000966504 SCV001113838 benign X-linked lymphoproliferative disease due to XIAP deficiency 2023-12-11 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000966504 SCV001328369 benign X-linked lymphoproliferative disease due to XIAP deficiency 2018-01-24 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002264113 SCV002543206 uncertain significance Autoinflammatory syndrome 2017-02-02 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000966504 SCV004563208 uncertain significance X-linked lymphoproliferative disease due to XIAP deficiency 2023-08-22 criteria provided, single submitter clinical testing The XIAP c.1408A>T; p.Thr470Ser variant (rs143165174) is reported in the literature in at least 3 individuals affected with X-linked lymphoproliferative syndrome-2 (XLP2) (Ashton 2016, Ashton 2020, Pachlopnik Schmid 2011). This variant is also reported in ClinVar (Variation ID: 784737). This variant is found in the general population with an overall allele frequency of 0.05% (95/205092 alleles, including 36 hemizygotes) and specifically in the non-Finnish European population with an allele frequency of 0.09% (79/92540 alleles, including 31 hemizygotes) in the Genome Aggregation Database. The threonine at codon 470 is weakly conserved, and computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.221). Due to limited information, the clinical significance of this variant is uncertain at this time. References: Ashton et al. Identification of Variants in Genes Associated with Single-gene Inflammatory Bowel Disease by Whole-exome Sequencing. Inflamm Bowel Dis. 2016 Oct;22(10):2317-27. PMID: 27537055. Ashton et al. Genetic Sequencing of Pediatric Patients Identifies Mutations in Monogenic Inflammatory Bowel Disease Genes that Translate to Distinct Clinical Phenotypes. Clin Transl Gastroenterol. 2020 Feb;11(2):e00129. PMID: 32463623. Pachlopnik Schmid et al. Clinical similarities and differences of patients with X-linked lymphoproliferative syndrome type 1 (XLP-1/SAP deficiency) versus type 2 (XLP-2/XIAP deficiency). Blood. 2011 Feb 3;117(5):1522-9. PMID: 21119115.

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