NM_020529.3(NFKBIA):c.437C>T (p.Thr146Ile) AND Ectodermal dysplasia and immunodeficiency 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 1, 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:: RCV000707277.9

Allele description [Variation Report for NM_020529.3(NFKBIA):c.437C>T (p.Thr146Ile)]

NM_020529.3(NFKBIA):c.437C>T (p.Thr146Ile)

Genes:

LOC130055494:ATAC-STARR-seq lymphoblastoid active region 8276 [Gene]
NFKBIA:NFKB inhibitor alpha [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q13.2

Genomic location:

Preferred name:

NM_020529.3(NFKBIA):c.437C>T (p.Thr146Ile)

HGVS:

NC_000014.9:g.35403260G>A
NG_007571.1:g.6479C>T
NM_020529.3:c.437C>TMANE SELECT
NP_065390.1:p.Thr146Ile
NP_065390.1:p.Thr146Ile
LRG_89t1:c.437C>T
LRG_89:g.6479C>T
LRG_89p1:p.Thr146Ile
NC_000014.8:g.35872466G>A
NM_020529.2:c.437C>T

Protein change:

T146I

Links:

dbSNP: rs753691609

NCBI 1000 Genomes Browser:

rs753691609

Molecular consequence:

NM_020529.3:c.437C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Ectodermal dysplasia and immunodeficiency 2
Synonyms:: Ectodermal dysplasia, anhidrotic, with T-cell immunodeficiency, autosomal dominant
Identifiers:: MONDO: MONDO:0012806; MedGen: C2677481; Orphanet: 238468; Orphanet: 98813; OMIM: 612132

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000836367	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 1, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000836367

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 1, 2023)

germline

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

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

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000836367.6

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

Description

This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 146 of the NFKBIA protein (p.Thr146Ile). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 583048). This variant has not been reported in the literature in individuals affected with NFKBIA-related conditions. This variant is present in population databases (rs753691609, gnomAD 0.01%).

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine