NM_000053.4(ATP7B):c.3298T>A (p.Cys1100Ser) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 22, 2018
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:: RCV000780932.1

Allele description [Variation Report for NM_000053.4(ATP7B):c.3298T>A (p.Cys1100Ser)]

NM_000053.4(ATP7B):c.3298T>A (p.Cys1100Ser)

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.3298T>A (p.Cys1100Ser)

HGVS:

NC_000013.11:g.51942500A>T
NG_008806.1:g.73995T>A
NM_000053.4:c.3298T>AMANE SELECT
NM_001005918.3:c.2677T>A
NM_001243182.2:c.2965T>A
NM_001330578.2:c.3064T>A
NM_001330579.2:c.3046T>A
NP_000044.2:p.Cys1100Ser
NP_001005918.1:p.Cys893Ser
NP_001230111.1:p.Cys989Ser
NP_001317507.1:p.Cys1022Ser
NP_001317508.1:p.Cys1016Ser
NC_000013.10:g.52516636A>T
NM_000053.3:c.3298T>A

Protein change:

C1016S

Links:

dbSNP: rs1566468882

NCBI 1000 Genomes Browser:

rs1566468882

Molecular consequence:

NM_000053.4:c.3298T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001005918.3:c.2677T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001243182.2:c.2965T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001330578.2:c.3064T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001330579.2:c.3046T>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

Recent activity

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trxA [Mycobacterium canettii CIPT 140010059]
trxA [Mycobacterium canettii CIPT 140010059]
Gene ID:45427914

Gene
45427914[uid] AND (alive[prop]) (1)
Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000918594	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Mar 22, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000918594

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Mar 22, 2018)

germline

clinical testing

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

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

Elucidation of the ATP7B N-domain Mg2+-ATP coordination site and its allosteric regulation.

Hercend C, Bauvais C, Bollot G, Delacotte N, Chappuis P, Woimant F, Launay JM, Manivet P.

PLoS One. 2011;6(10):e26245. doi: 10.1371/journal.pone.0026245. Epub 2011 Oct 27.

PubMed [citation]

PMID:: 22046264
PMCID:: PMC3203118

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000918594.1

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

Description

Variant summary: ATP7B c.3298T>A (p.Cys1100Ser) results in a non-conservative amino acid change located in the nucleotide binding domain of the protein (Hercend 2011). Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 246238 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.3298T>A in individuals affected with Wilson Disease and no experimental evidence demonstrating its impact on protein function have been reported. Co-occurrence with two other pathogenic ATP7B variants has been reported in our internal database in one specimen (c.2304dupC / c.3301_3302insCCAGGCAGTGCCAG, p.Met769fsX26 / p.Gly1101fsX25), providing supporting evidence for a benign role (though the phase was not characterized). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.

#	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: Nov 5, 2022

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