NM_000383.4(AIRE):c.1095+1G>C AND Polyglandular autoimmune syndrome, type 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 13, 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:: RCV003523638.3

Allele description [Variation Report for NM_000383.4(AIRE):c.1095+1G>C]

NM_000383.4(AIRE):c.1095+1G>C

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.1095+1G>C

HGVS:

NC_000021.9:g.44292402G>C
NG_009556.1:g.11523G>C
NM_000383.4:c.1095+1G>CMANE SELECT
LRG_18:g.11523G>C
NC_000021.8:g.45712285G>C

Links:

dbSNP: rs1022025101

NCBI 1000 Genomes Browser:

rs1022025101

Molecular consequence:

NM_000383.4:c.1095+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]

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
SCV004304798	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 13, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 27105486, 31420020, 16199547, 11524731, 26141571, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004304798

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 13, 2023)

germline

clinical testing

PubMed (6)
[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

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy: report of three cases from Iran.

Seifi-Alan M, Shamsi R, Setoodeh A, Sayarifard F, Aghasi P, Kompani F, Ghafouri-Fard S, Abbasi F.

J Pediatr Endocrinol Metab. 2016 Aug 1;29(8):979-83. doi: 10.1515/jpem-2016-0017.

PubMed [citation]

PMID:: 27105486

Autoimmune Polyglandular Syndrome Type 1: a case report.

Sajjadi-Jazi SM, Soltani A, Enayati S, Kakavand Hamidi A, Amoli MM.

BMC Med Genet. 2019 Aug 16;20(1):143. doi: 10.1186/s12881-019-0870-3.

PubMed [citation]

PMID:: 31420020
PMCID:: PMC6698041

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004304798.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Disruption of this splice site has been observed in individuals with autosomal recessive autoimmune polyendocrinopathy syndrome (PMID: 27105486, 31420020). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 9 of the AIRE gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in AIRE are known to be pathogenic (PMID: 11524731, 26141571).

#	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: May 16, 2025

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