NM_000383.4(AIRE):c.755C>T (p.Pro252Leu) AND Polyglandular autoimmune syndrome, type 1

Germline classification:: Benign/Likely benign (5 submissions)
Last evaluated:: Jan 31, 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:: RCV000029316.18

Allele description [Variation Report for NM_000383.4(AIRE):c.755C>T (p.Pro252Leu)]

NM_000383.4(AIRE):c.755C>T (p.Pro252Leu)

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.755C>T (p.Pro252Leu)

HGVS:

NC_000021.9:g.44289759C>T
NG_009556.1:g.8880C>T
NM_000383.4:c.755C>TMANE SELECT
NP_000374.1:p.Pro252Leu
LRG_18t1:c.755C>T
LRG_18:g.8880C>T
NC_000021.8:g.45709642C>T
NM_000383.2:c.755C>T
NM_000383.3:c.755C>T
O43918:p.Pro252Leu

Protein change:

P252L

Links:

UniProtKB: O43918#VAR_026484; dbSNP: rs34397615

NCBI 1000 Genomes Browser:

rs34397615

Molecular consequence:

NM_000383.4:c.755C>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; 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
SCV000051962	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	likely benign (Aug 18, 2011)	germline	curation, clinical testing	PubMed (6) [See all records that cite these PMIDs] 18399903, 18713028, 16114041, 18728167, 15511668, 11836330 Citation Link,
SCV000220138	Counsyl	criteria provided, single submitter (Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))	Likely benign (Mar 3, 2014)	unknown	literature only	PubMed (2) [See all records that cite these PMIDs] 11836330, 16114041 Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015), Citation Link,
SCV000629958	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Benign (Jan 31, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001460107	Natera, Inc.	no assertion criteria provided	Benign (Jun 17, 2020)	germline	clinical testing
SCV002801166	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Apr 25, 2022)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	1	not provided	curation
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing, literature only

Citations

PubMed

Innate and adaptive immunity in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy.

Perniola R, Congedo M, Rizzo A, Sticchi Damiani A, Faneschi ML, Pizzolante M, Lobreglio G.

Mycoses. 2008 May;51(3):228-35. doi: 10.1111/j.1439-0507.2007.01475.x.

PubMed [citation]

PMID:: 18399903

High prevalence of thyroid autoimmunity in Apulian patients with autoimmune polyglandular syndrome type 1.

Perniola R, Filograna O, Greco G, Pellegrino V.

Thyroid. 2008 Sep;18(9):1027-9. doi: 10.1089/thy.2008.0027. No abstract available.

PubMed [citation]

PMID:: 18713028

See all PubMed Citations (8)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000051962.2

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

Description

"Patient #9, female, diagnosed with APS1, is compound heterozygous for the variant (paternally inherited) and W78R (maternally inherited); father of the proband is a carrier of the variant and asymptomatic; authors suggest that the variant is located in the SAND domain, likely a DNA-binding motif and that the “proline-leucine substitution can be considered a nonconservative change, probably resulting in the destruction of the basal coil secondary structure of the gene related to its proline-rich composition”; variant not detected in controls (see pbGP).": PubMed [ID: 11836330]

Description

Converted during submission to Likely benign.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided
2	germline	unknown	not provided	Blood	assert pathogenicity		not provided	not provided	not provided	See 2

Co-occurrences

#	Zygosity	Alleles	Number of Observations
2	SingleHeterozygote	AIRE:c.99T>C, AIRE:c.834C>G, AIRE:c.1197T>C, AIRE:c.1578T>C, AIRE:c.1296G>A, AIRE:c.1203T>C	1

From Counsyl, SCV000220138.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000629958.8

#	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 Natera, Inc., SCV001460107.1

#	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	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Fulgent Genetics, Fulgent Genetics, SCV002801166.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 20, 2024

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