Submissions for variant NM_000383.4(AIRE):c.173C>G (p.Ala58Gly)

dbSNP: rs747941115

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002022142	SCV002257780	likely pathogenic	Polyglandular autoimmune syndrome, type 1	2022-06-07	criteria provided, single submitter	clinical testing	This variant disrupts the p.Ala58 amino acid residue in AIRE. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 26114819, 28911151, 30003128). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt AIRE protein function. This missense change has been observed in individual(s) with clinical features of autoimmune polyendocrinopathy syndrome (Invitae). This variant is present in population databases (rs747941115, gnomAD 0.0009%). This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 58 of the AIRE protein (p.Ala58Gly).