ClinVar Miner

Submissions for variant NM_000383.4(AIRE):c.46A>G (p.Thr16Ala)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003045755 SCV003330587 likely pathogenic Polyglandular autoimmune syndrome, type 1 2022-03-13 criteria provided, single submitter clinical testing 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. This variant disrupts the p.Thr16 amino acid residue in AIRE. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11524733, 21932610, 25361846, 28911151). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 variant has not been reported in the literature in individuals affected with AIRE-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 16 of the AIRE protein (p.Thr16Ala).

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