NM_000383.4(AIRE):c.1066C>T (p.Arg356Trp) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 1, 2021
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:: RCV001532961.1

Allele description [Variation Report for NM_000383.4(AIRE):c.1066C>T (p.Arg356Trp)]

NM_000383.4(AIRE):c.1066C>T (p.Arg356Trp)

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.1066C>T (p.Arg356Trp)

HGVS:

NC_000021.9:g.44292372C>T
NG_009556.1:g.11493C>T
NM_000383.4:c.1066C>TMANE SELECT
NP_000374.1:p.Arg356Trp
LRG_18:g.11493C>T
NC_000021.8:g.45712255C>T
NM_000383.3:c.1066C>T

Protein change:

R356W

Links:

dbSNP: rs376901046

NCBI 1000 Genomes Browser:

rs376901046

Molecular consequence:

NM_000383.4:c.1066C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001748782	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Jul 1, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 32441320, 26650942 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001748782

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Jul 1, 2021)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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

Next generation sequencing analysis of consecutive Russian patients with clinical suspicion of inborn errors of immunity.

Suspitsin EN, Guseva MN, Kostik MM, Sokolenko AP, Skripchenko NV, Levina AS, Goleva OV, Dubko MF, Tumakova AV, Makhova MA, Lyazina LV, Bizin IV, Sokolova NE, Gabrusskaya TV, Ditkovskaya LV, Kozlova OP, Vahliarskaya SS, Kondratenko IV, Imyanitov EN.

Clin Genet. 2020 Sep;98(3):231-239. doi: 10.1111/cge.13789. Epub 2020 Jun 17.

PubMed [citation]

PMID:: 32441320

Primary Adrenocortical Insufficiency Case Series: Genetic Etiologies More Common than Expected.

Tsai SL, Green J, Metherell LA, Curtis F, Fernandez B, Healey A, Curtis J.

Horm Res Paediatr. 2016;85(1):35-42. doi: 10.1159/000441843. Epub 2015 Dec 10.

PubMed [citation]

PMID:: 26650942

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001748782.1

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

Description

Variant summary: AIRE c.1066C>T (p.Arg356Trp) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00014 in 162232 control chromosomes (gnomAD). This frequency is not higher than expected for a pathogenic variant in AIRE causing Autoimmune Polyglandular Syndrome Type 1 (0.00014 vs 0.0028), allowing no conclusion about variant significance. c.1066C>T has been reported in the literature in individuals affected with Autoimmune Polyglandular Syndrome Type 1 (e.g. Tsai_2016, Suspitsin_2020). These reports do not provide unequivocal conclusions about association of the variant with Autoimmune Polyglandular Syndrome Type 1. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

#	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: Oct 13, 2024

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