NM_000383.4(AIRE):c.1616C>T (p.Pro539Leu) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Mar 6, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000059052.8

Allele description [Variation Report for NM_000383.4(AIRE):c.1616C>T (p.Pro539Leu)]

NM_000383.4(AIRE):c.1616C>T (p.Pro539Leu)

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.1616C>T (p.Pro539Leu)

HGVS:

NC_000021.9:g.44297705C>T
NG_009556.1:g.16826C>T
NG_034033.1:g.2672C>T
NM_000383.4:c.1616C>TMANE SELECT
NP_000374.1:p.Pro539Leu
LRG_18t1:c.1616C>T
LRG_18:g.16826C>T
NC_000021.8:g.45717588C>T
NM_000383.2:c.1616C>T
NM_000383.3:c.1616C>T
O43918:p.Pro539Leu

Protein change:

P539L

Links:

UniProtKB: O43918#VAR_026486; UniProtKB/Swiss-Prot: VAR_026486; dbSNP: rs179363889

NCBI 1000 Genomes Browser:

rs179363889

Molecular consequence:

NM_000383.4:c.1616C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000090573	UniProtKB/Swiss-Prot	no classification provided	not provided	germline	not provided	PubMed (1) [See all records that cite this PMID]
SCV000329058	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Mar 6, 2024)	germline	clinical testing	Citation Link,
SCV000927331	Blueprint Genetics	criteria provided, single submitter (Blueprint Genetics Variant Classification Scheme)	Pathogenic (Jul 10, 2017)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000090573

UniProtKB/Swiss-Prot

no classification provided

not provided

germline

not provided

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

SCV000329058

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Mar 6, 2024)

germline

clinical testing

Citation Link,

SCV000927331

Blueprint Genetics

criteria provided, single submitter

(Blueprint Genetics Variant Classification Scheme)

Pathogenic
(Jul 10, 2017)

germline

clinical testing

Citation Link

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	not provided	not provided	not provided	not provided	1	not provided	literature only

Citations

PubMed

Delineation of the molecular defects in the AIRE gene in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy patients from Southern Italy.

Meloni A, Perniola R, Faà V, Corvaglia E, Cao A, Rosatelli MC.

J Clin Endocrinol Metab. 2002 Feb;87(2):841-6.

PubMed [citation]

PMID:: 11836330

Details of each submission

From UniProtKB/Swiss-Prot, SCV000090573.1

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

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

From GeneDx, SCV000329058.7

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

Description

Published functional studies demonstrate a reduction of transactivation activity compared to normal protein (PMID: 17675238); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 21295522, 30018023, 15511668, 28446514, 23000069, 12398240, 17289071, 18713028, 15751604, 11836330, 15811934, 34846681, 17675238)

#	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

From Blueprint Genetics, SCV000927331.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	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	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 16, 2025

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