NM_000593.6(TAP1):c.1937G>A (p.Gly646Asp) AND MHC class I deficiency

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

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Dec 17, 2023
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:: RCV001824252.3

Allele description

NM_000593.6(TAP1):c.1937G>A (p.Gly646Asp)

Gene:

TAP1:transporter 1, ATP binding cassette subfamily B member [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p21.32

Genomic location:

Preferred name:

NM_000593.6(TAP1):c.1937G>A (p.Gly646Asp)

HGVS:

NC_000006.12:g.32847171C>T
NG_011759.1:g.11801G>A
NG_028165.1:g.2765G>A
NM_000593.6:c.1937G>AMANE SELECT
NM_001292022.2:c.1334G>A
NP_000584.3:p.Gly646Asp
NP_001278951.1:p.Gly445Asp
LRG_166t1:c.1937G>A
LRG_1328:g.2765G>A
LRG_166:g.11801G>A
LRG_166p1:p.Gly646Asp
NC_000006.11:g.32814948C>T

Protein change:

G445D

Links:

dbSNP: rs765527607

NCBI 1000 Genomes Browser:

rs765527607

Molecular consequence:

NM_000593.6:c.1937G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001292022.2:c.1334G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: MHC class I deficiency
Synonyms:: BARE LYMPHOCYTE SYNDROME, TYPE I; BLS, TYPE I
Identifiers:: MONDO: MONDO:0011476; MedGen: C1858266; Orphanet: 34592; OMIM: PS604571

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002073892	Genomics Facility, Ludwig-Maximilians-Universität München	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Dec 28, 2021)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004477054	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 17, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 15897556, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002073892

Genomics Facility, Ludwig-Maximilians-Universität München

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Dec 28, 2021)

unknown

clinical testing

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

SCV004477054

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 17, 2023)

germline

clinical testing

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

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

Citations

PubMed

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

A rare transporter associated with antigen processing polymorphism overpresented in HLAlow colon cancer reveals the functional significance of the signature domain in antigen processing.

Yang T, Lapinski PE, Zhao H, Zhou Q, Zhang H, Raghavan M, Liu Y, Zheng P.

Clin Cancer Res. 2005 May 15;11(10):3614-23.

PubMed [citation]

PMID:: 15897556

See all PubMed Citations (3)

Details of each submission

From Genomics Facility, Ludwig-Maximilians-Universität München, SCV002073892.1

#	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	yes	not provided	PBMCs	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV004477054.1

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

Description

This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 706 of the TAP1 protein (p.Gly706Asp). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with TAP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1339543). 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. Experimental studies have shown that this missense change affects TAP1 function (PMID: 15897556). 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: Jun 23, 2024

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