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NM_000383.4(AIRE):c.269A>G (p.Tyr90Cys) AND Polyglandular autoimmune syndrome, type 1

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 27, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV003522923.3

Allele description [Variation Report for NM_000383.4(AIRE):c.269A>G (p.Tyr90Cys)]

NM_000383.4(AIRE):c.269A>G (p.Tyr90Cys)

Gene:
AIRE:autoimmune regulator [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
21q22.3
Genomic location:
Preferred name:
NM_000383.4(AIRE):c.269A>G (p.Tyr90Cys)
HGVS:
  • NC_000021.9:g.44286693A>G
  • NG_009556.1:g.5814A>G
  • NM_000383.4:c.269A>GMANE SELECT
  • NP_000374.1:p.Tyr90Cys
  • LRG_18t1:c.269A>G
  • LRG_18:g.5814A>G
  • NC_000021.8:g.45706576A>G
  • NM_000383.2:c.269A>G
  • O43918:p.Tyr90Cys
Protein change:
Y90C
Links:
UniProtKB: O43918#VAR_013719; UniProtKB/Swiss-Prot: VAR_013719; dbSNP: rs179363883
NCBI 1000 Genomes Browser:
rs179363883
Molecular consequence:
  • NM_000383.4:c.269A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Polyglandular autoimmune syndrome, type 1 (APS1)
Synonyms:
AUTOIMMUNE POLYENDOCRINE SYNDROME, TYPE I, WITH OR WITHOUT REVERSIBLE METAPHYSEAL DYSPLASIA; APS I; HYPOADRENOCORTICISM WITH HYPOPARATHYROIDISM AND SUPERFICIAL MONILIASIS; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009411; MedGen: C0085859; Orphanet: 3453; OMIM: 240300

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004297415Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jun 27, 2023) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

A common and recurrent 13-bp deletion in the autoimmune regulator gene in British kindreds with autoimmune polyendocrinopathy type 1.

Pearce SH, Cheetham T, Imrie H, Vaidya B, Barnes ND, Bilous RW, Carr D, Meeran K, Shaw NJ, Smith CS, Toft AD, Williams G, Kendall-Taylor P.

Am J Hum Genet. 1998 Dec;63(6):1675-84.

PubMed [citation]
PMID:
9837820
PMCID:
PMC1377639

Characterization of the clinical and genetic spectrum of autoimmune polyendocrine syndrome type 1 in Chinese case series.

Wang YB, Wang O, Nie M, Jiang Y, Li M, Xia WB, Xing XP.

Orphanet J Rare Dis. 2021 Jul 3;16(1):296. doi: 10.1186/s13023-021-01933-y.

PubMed [citation]
PMID:
34217342
PMCID:
PMC8254246
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004297415.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 68223). This missense change has been observed in individual(s) with autoimmune polyendocrine syndrome type 1 (PMID: 9837820, 34217342). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs179363883, gnomAD 0.009%), including at least one homozygous and/or hemizygous individual. This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 90 of the AIRE protein (p.Tyr90Cys).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 16, 2025