Submissions for variant NM_000383.4(AIRE):c.47C>G (p.Thr16Arg)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004587984	SCV005075820	likely pathogenic	Polyglandular autoimmune syndrome, type 1	2024-04-03	criteria provided, single submitter	clinical testing	Variant summary: AIRE c.47C>G (p.Thr16Arg) results in a non-conservative amino acid change located in the HSR domain (IPR004865) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent from 135998 control chromosomes. c.47C>G has been reported in the literature in at least one homozygous individual affected with Autoimmune Polyglandular Syndrome Type 1 (e.g. Yan_2020). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A different variant located at the same codon (c.347C>T, p.Thr16Met) has been classified as pathogenic, supporting a critical relevance of this residue to AIRE protein function. The following publication has been ascertained in the context of this evaluation (PMID: 32358377). No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as likely pathogenic.