NM_000053.4(ATP7B):c.3452G>A (p.Arg1151His) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 30, 2016
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:: RCV000586771.1

Allele description [Variation Report for NM_000053.4(ATP7B):c.3452G>A (p.Arg1151His)]

NM_000053.4(ATP7B):c.3452G>A (p.Arg1151His)

Gene:

ATP7B:ATPase copper transporting beta [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

13q14.3

Genomic location:

Preferred name:

NM_000053.4(ATP7B):c.3452G>A (p.Arg1151His)

HGVS:

NC_000013.11:g.51941185C>T
NG_008806.1:g.75310G>A
NM_000053.4:c.3452G>AMANE SELECT
NM_001005918.3:c.2831G>A
NM_001243182.2:c.3119G>A
NM_001330578.2:c.3218G>A
NM_001330579.2:c.3200G>A
NP_000044.2:p.Arg1151His
NP_001005918.1:p.Arg944His
NP_001230111.1:p.Arg1040His
NP_001317507.1:p.Arg1073His
NP_001317508.1:p.Arg1067His
NC_000013.10:g.52515321C>T
NM_000053.2:c.3452G>A
NM_000053.3:c.3452G>A

Protein change:

R1040H

Links:

dbSNP: rs377297166

NCBI 1000 Genomes Browser:

rs377297166

Molecular consequence:

NM_000053.4:c.3452G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001005918.3:c.2831G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001243182.2:c.3119G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001330578.2:c.3218G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001330579.2:c.3200G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000694447	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Aug 30, 2016)	germline	clinical testing	PubMed (10) [See all records that cite these PMIDs] 15205462, 18203200, 24253677, 22308153, 10544227, 16233999, 21219664, 16495228, 27022412, 17680703 LabCorp Variant Classification Summary - May 2015.docx Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000694447

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Aug 30, 2016)

germline

clinical testing

PubMed (10)
[See all records that cite these PMIDs]

LabCorp Variant Classification Summary - May 2015.docx

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

The distinct functional properties of the nucleotide-binding domain of ATP7B, the human copper-transporting ATPase: analysis of the Wilson disease mutations E1064A, H1069Q, R1151H, and C1104F.

Morgan CT, Tsivkovskii R, Kosinsky YA, Efremov RG, Lutsenko S.

J Biol Chem. 2004 Aug 27;279(35):36363-71. Epub 2004 Jun 17.

PubMed [citation]

PMID:: 15205462

Sequence variation in the ATP-binding domain of the Wilson disease transporter, ATP7B, affects copper transport in a yeast model system.

Hsi G, Cullen LM, Macintyre G, Chen MM, Glerum DM, Cox DW.

Hum Mutat. 2008 Apr;29(4):491-501. doi: 10.1002/humu.20674.

PubMed [citation]

PMID:: 18203200

See all PubMed Citations (10)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000694447.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (10)

Description

Variant summary: The ATP7B c.3452G>A (p.Arg1151His) variant involves the alteration of a conserved nucleotide and this variant is located in the P-type ATPase and/or cytoplasmic domain N which is critical for ATP binding. 5/5 in silico tools predict a damaging outcome for this variant. This variant was found in 2/120874 control chromosomes at a frequency of 0.0000165, which does not exceed the estimated maximal expected allele frequency of a pathogenic ATP7B variant (0.0054006). This variant has been reported in at least 3 WD patients (Loudianos_1999, Li_2011, Dong_2016), one was mentioned to be compound heterozygotes of this variant and Gly1089Glu. One internal sample carries this variant and a pathogenic variant (p.His1069Gln); clinical status as well as phase of the variants unknown. One in vitro study showed that this variant mildly affects the structure and ATP-binding activity of ATP7B protein using N-domain fragment (Morgan_2004). In addition, one reputable database classified this variant as disease variant. Taken together, this variant is classified as VUS-possibly pathogenic.

#	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

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