ClinVar Miner

Submissions for variant NM_000383.4(AIRE):c.463G>A (p.Gly155Ser)

gnomAD frequency: 0.00001  dbSNP: rs193922418
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000029313 SCV000051959 likely pathogenic Polyglandular autoimmune syndrome, type 1 2011-08-18 criteria provided, single submitter curation Converted during submission to Likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV000029313 SCV002181175 pathogenic Polyglandular autoimmune syndrome, type 1 2023-10-05 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 155 of the AIRE protein (p.Gly155Ser). RNA analysis indicates that this missense change induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal recessive autoimmune polyendocrinopathy syndrome (PMID: 19209622, 23342054). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 35665). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this missense change alters mRNA splicing and is expected to lead to the loss of protein expression (PMID: 23342054). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV000029313 SCV002815375 likely pathogenic Polyglandular autoimmune syndrome, type 1 2021-08-20 criteria provided, single submitter clinical testing
National Institute of Allergy and Infectious Diseases - Centralized Sequencing Program, National Institutes of Health RCV000029313 SCV004036199 pathogenic Polyglandular autoimmune syndrome, type 1 2023-09-14 criteria provided, single submitter clinical testing

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