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NM_000383.4(AIRE):c.865C>A (p.Pro289Thr) AND Polyglandular autoimmune syndrome, type 1

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Sep 15, 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:
RCV003637423.1

Allele description [Variation Report for NM_000383.4(AIRE):c.865C>A (p.Pro289Thr)]

NM_000383.4(AIRE):c.865C>A (p.Pro289Thr)

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.865C>A (p.Pro289Thr)
HGVS:
  • NC_000021.9:g.44290054C>A
  • NG_009556.1:g.9175C>A
  • NM_000383.4:c.865C>AMANE SELECT
  • NP_000374.1:p.Pro289Thr
  • NP_000374.1:p.Pro289Thr
  • LRG_18t1:c.865C>A
  • LRG_18:g.9175C>A
  • LRG_18p1:p.Pro289Thr
  • NC_000021.8:g.45709937C>A
  • NM_000383.2:c.865C>A
Protein change:
P289T
Molecular consequence:
  • NM_000383.4:c.865C>A - 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; PGA I; 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
SCV004549875Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Sep 15, 2023) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV004549875.1

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

Description

This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 289 of the AIRE protein (p.Pro289Thr). This variant has not been reported in the literature in individuals affected with AIRE-related conditions. 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. 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 not expected to disrupt AIRE protein function.

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

Last Updated: May 12, 2024