NM_001167.4(XIAP):c.492A>T (p.Glu164Asp) AND X-linked lymphoproliferative disease due to XIAP deficiency

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 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:: RCV003625610.1

Allele description

NM_001167.4(XIAP):c.492A>T (p.Glu164Asp)

Gene:

XIAP:X-linked inhibitor of apoptosis [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq25

Genomic location:

Preferred name:

NM_001167.4(XIAP):c.492A>T (p.Glu164Asp)

HGVS:

NC_000023.11:g.123886154A>T
NG_007264.1:g.30957A>T
NM_001167.4:c.492A>TMANE SELECT
NM_001204401.2:c.492A>T
NM_001378590.1:c.492A>T
NM_001378591.1:c.492A>T
NM_001378592.1:c.492A>T
NP_001158.2:p.Glu164Asp
NP_001158.2:p.Glu164Asp
NP_001191330.1:p.Glu164Asp
NP_001365519.1:p.Glu164Asp
NP_001365520.1:p.Glu164Asp
NP_001365521.1:p.Glu164Asp
LRG_19t1:c.492A>T
LRG_19:g.30957A>T
LRG_19p1:p.Glu164Asp
NC_000023.10:g.123020004A>T
NM_001167.3:c.492A>T

Protein change:

E164D

Molecular consequence:

NM_001167.4:c.492A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001204401.2:c.492A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001378590.1:c.492A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001378591.1:c.492A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001378592.1:c.492A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: X-linked lymphoproliferative disease due to XIAP deficiency
Synonyms:: XIAP DEFICIENCY; Lymphoproliferative syndrome 2, X-linked
Identifiers:: MONDO: MONDO:0010385; MedGen: C1845076; Orphanet: 2442; OMIM: 300635

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004435645	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 13, 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

SCV004435645

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 13, 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 Invitae, SCV004435645.1

#	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 glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 164 of the XIAP protein (p.Glu164Asp). This variant is present in population databases (no rsID available, gnomAD 0.001%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with XIAP-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt XIAP protein function. 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.

#	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 1, 2024

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