ClinVar Miner

Submissions for variant NM_000383.4(AIRE):c.1295C>T (p.Ala432Val)

gnomAD frequency: 0.00001  dbSNP: rs531220961
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001916850 SCV002192516 uncertain significance Polyglandular autoimmune syndrome, type 1 2022-08-22 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 432 of the AIRE protein (p.Ala432Val). This variant is present in population databases (rs531220961, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with AIRE-related conditions. ClinVar contains an entry for this variant (Variation ID: 1421295). 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"). 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.
PreventionGenetics, part of Exact Sciences RCV003407955 SCV004115246 uncertain significance AIRE-related disorder 2023-05-09 criteria provided, single submitter clinical testing The AIRE c.1295C>T variant is predicted to result in the amino acid substitution p.Ala432Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0063% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/21-45713688-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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