NM_001167.4(XIAP):c.778C>T (p.Pro260Ser) AND X-linked lymphoproliferative disease due to XIAP deficiency

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Sep 20, 2024
Review status:: criteria provided, conflicting classifications

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:: RCV001961730.7

Allele description [Variation Report for NM_001167.4(XIAP):c.778C>T (p.Pro260Ser)]

NM_001167.4(XIAP):c.778C>T (p.Pro260Ser)

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.778C>T (p.Pro260Ser)

HGVS:

NC_000023.11:g.123886440C>T
NG_007264.1:g.31243C>T
NM_001167.4:c.778C>TMANE SELECT
NM_001204401.2:c.778C>T
NM_001378590.1:c.778C>T
NM_001378591.1:c.778C>T
NM_001378592.1:c.778C>T
NP_001158.2:p.Pro260Ser
NP_001191330.1:p.Pro260Ser
NP_001365519.1:p.Pro260Ser
NP_001365520.1:p.Pro260Ser
NP_001365521.1:p.Pro260Ser
LRG_19:g.31243C>T
NC_000023.10:g.123020290C>T

Protein change:

P260S

Links:

dbSNP: rs2148090201

NCBI 1000 Genomes Browser:

rs2148090201

Molecular consequence:

NM_001167.4:c.778C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001204401.2:c.778C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001378590.1:c.778C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001378591.1:c.778C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001378592.1:c.778C>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
SCV002252616	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 5, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005329069	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Sep 20, 2024)	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

SCV002252616

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 5, 2022)

germline

clinical testing

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

SCV005329069

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely benign
(Sep 20, 2024)

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
not provided	germline	no	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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002252616.3

#	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 proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 260 of the XIAP protein (p.Pro260Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with XIAP-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). 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

From 3billion, SCV005329069.1

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

Description

The hemizygous variant was found in patients with no symptoms related to the gene containing the hemizygous variant.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 8, 2024

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