NM_000383.4(AIRE):c.1322C>T (p.Thr441Met) AND Polyglandular autoimmune syndrome, type 1

Germline classification:: Conflicting classifications of pathogenicity (5 submissions)
Last evaluated:: Feb 2, 2025
Review status:: criteria provided, conflicting classifications

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:: RCV000957765.17

Allele description [Variation Report for NM_000383.4(AIRE):c.1322C>T (p.Thr441Met)]

NM_000383.4(AIRE):c.1322C>T (p.Thr441Met)

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.1322C>T (p.Thr441Met)

HGVS:

NC_000021.9:g.44293832C>T
NG_009556.1:g.12953C>T
NM_000383.4:c.1322C>TMANE SELECT
NP_000374.1:p.Thr441Met
LRG_18t1:c.1322C>T
LRG_18:g.12953C>T
NC_000021.8:g.45713715C>T
NM_000383.2:c.1322C>T
NM_000383.3:c.1322C>T

Protein change:

T441M

Links:

dbSNP: rs72650677

NCBI 1000 Genomes Browser:

rs72650677

Molecular consequence:

NM_000383.4:c.1322C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001104583	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Benign (Feb 2, 2025)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001423241	GenomeConnect, ClinGen	no classification provided	not provided	unknown	phenotyping only
SCV001622932	New York Genome Center - CSER-NYCKidSeq	criteria provided, single submitter (NYGC Assertion Criteria 2020)	Uncertain significance (Jul 9, 2020)	inherited	clinical testing	Citation Link,
SCV001737193	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (May 18, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004036195	National Institute of Allergy and Infectious Diseases - Centralized Sequencing Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Sep 14, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 17101293, 30290665, 34426522, 25741868

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	inherited	unknown	1	not provided	not provided	1	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	phenotyping only

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. doi: 10.1038/s41436-019-0624-9..

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

AIRE gene polymorphisms in systemic sclerosis associated with autoimmune thyroiditis.

Ferrera F, Rizzi M, Sprecacenere B, Balestra P, Sessarego M, Di Carlo A, Filaci G, Gabrielli A, Ravazzolo R, Indiveri F.

Clin Immunol. 2007 Jan;122(1):13-7. Epub 2006 Nov 13.

PubMed [citation]

PMID:: 17101293

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001104583.7

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

#	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

From GenomeConnect, ClinGen, SCV001423241.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	phenotyping only	not provided

Description

Variant interpretted as Uncertain significance and reported on 01-09-2019 by Lab or GTR ID 1238. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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

From New York Genome Center - CSER-NYCKidSeq, SCV001622932.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

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

From Genome-Nilou Lab, SCV001737193.2

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From National Institute of Allergy and Infectious Diseases - Centralized Sequencing Program, National Institutes of Health, SCV004036195.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

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

Last Updated: Apr 20, 2025

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