ClinVar Miner

Submissions for variant NM_000383.4(AIRE):c.983G>A (p.Arg328Gln)

gnomAD frequency: 0.00001  dbSNP: rs775921321
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000816768 SCV000957293 uncertain significance Polyglandular autoimmune syndrome, type 1 2022-08-29 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 328 of the AIRE protein (p.Arg328Gln). This variant is present in population databases (rs775921321, gnomAD 0.02%). This missense change has been observed in individual(s) with acrofacial vitiligo (PMID: 26084028). ClinVar contains an entry for this variant (Variation ID: 659723). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Experimental studies have shown that this missense change affects AIRE function (PMID: 26084028). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.