NM_000383.4(AIRE):c.2T>C (p.Met1Thr) AND Polyglandular autoimmune syndrome, type 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 5, 2022
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:: RCV003064634.3

Allele description [Variation Report for NM_000383.4(AIRE):c.2T>C (p.Met1Thr)]

NM_000383.4(AIRE):c.2T>C (p.Met1Thr)

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.2T>C (p.Met1Thr)

HGVS:

NC_000021.9:g.44286008T>C
NG_009556.1:g.5129T>C
NM_000383.4:c.2T>CMANE SELECT
NP_000374.1:p.Met1Thr
NP_000374.1:p.Met1Thr
LRG_18t1:c.2T>C
LRG_18:g.5129T>C
LRG_18p1:p.Met1Thr
NC_000021.8:g.45705891T>C
NM_000383.2:c.2T>C

Protein change:

M1T

Molecular consequence:

NM_000383.4:c.2T>C - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_000383.4:c.2T>C - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003444517	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 5, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 16965330, 19758376, 28446514, 28911151, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003444517

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 5, 2022)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Molecular background of polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome in a Polish population: novel AIRE mutations and an estimate of disease prevalence.

Stolarski B, Pronicka E, Korniszewski L, Pollak A, Kostrzewa G, Rowińska E, Włodarski P, Skórka A, Gremida M, Krajewski P, Ploski R.

Clin Genet. 2006 Oct;70(4):348-54.

PubMed [citation]

PMID:: 16965330

Novel and recurrent mutations in the AIRE gene of autoimmune polyendocrinopathy syndrome type 1 (APS1) patients.

Faiyaz-Ul-Haque M, Bin-Abbas B, Al-Abdullatif A, Abdullah Abalkhail H, Toulimat M, Al-Gazlan S, Almutawa AM, Al-Sagheir A, Peltekova I, Al-Dayel F, Zaidi SH.

Clin Genet. 2009 Nov;76(5):431-40. doi: 10.1111/j.1399-0004.2009.01278.x. Epub 2009 Sep 15.

PubMed [citation]

PMID:: 19758376

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003444517.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change affects the initiator methionine of the AIRE mRNA. The next in-frame methionine is located at codon 184. For these reasons, this variant has been classified as Pathogenic. Disruption of the initiator codon has been observed in individual(s) with autosomal recessive autoimmune polyendocrinopathy syndrome (PMID: 16965330, 19758376, 28446514, 28911151). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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