ClinVar Miner

Submissions for variant NM_000383.4(AIRE):c.166C>T (p.Pro56Ser)

gnomAD frequency: 0.00004  dbSNP: rs753460287
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000812156 SCV000952460 uncertain significance Polyglandular autoimmune syndrome, type 1 2021-08-31 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 56 of the AIRE protein (p.Pro56Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. This variant is present in population databases (rs753460287, ExAC 0.05%). 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000812156 SCV003919848 uncertain significance Polyglandular autoimmune syndrome, type 1 2021-03-30 criteria provided, single submitter clinical testing AIRE NM_000383.3 exon 2 p.Pro56Ser (c.166C>T): This variant has not been reported in the literature but is present in 0.03% (8/25114) of Finnish alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/21-45706473-C-T?dataset=gnomad_r2_1). This variant is present in ClinVar (Variation ID:655886). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Ambry Genetics RCV004028760 SCV004880769 uncertain significance Inborn genetic diseases 2022-10-06 criteria provided, single submitter clinical testing The c.166C>T (p.P56S) alteration is located in exon 2 (coding exon 2) of the AIRE gene. This alteration results from a C to T substitution at nucleotide position 166, causing the proline (P) at amino acid position 56 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV000812156 SCV002083844 uncertain significance Polyglandular autoimmune syndrome, type 1 2020-11-06 no assertion criteria provided clinical testing

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