ClinVar Miner

Submissions for variant NM_000383.4(AIRE):c.1348G>A (p.Ala450Thr)

gnomAD frequency: 0.00004  dbSNP: rs758446796
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001247650 SCV001421086 uncertain significance Polyglandular autoimmune syndrome, type 1 2021-08-26 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 450 of the AIRE protein (p.Ala450Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs758446796, ExAC 0.005%). This variant has not been reported in the literature in individuals affected with AIRE-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
PreventionGenetics, part of Exact Sciences RCV003414070 SCV004118203 uncertain significance AIRE-related disorder 2023-06-02 criteria provided, single submitter clinical testing The AIRE c.1348G>A variant is predicted to result in the amino acid substitution p.Ala450Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.017% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/21-45713741-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Natera, Inc. RCV001247650 SCV002076126 uncertain significance Polyglandular autoimmune syndrome, type 1 2020-02-26 no assertion criteria provided clinical testing

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