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NM_000053.4(ATP7B):c.3452G>C (p.Arg1151Pro) AND Wilson disease

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Apr 11, 2022
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV002227383.8

Allele description [Variation Report for NM_000053.4(ATP7B):c.3452G>C (p.Arg1151Pro)]

NM_000053.4(ATP7B):c.3452G>C (p.Arg1151Pro)

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>C (p.Arg1151Pro)
HGVS:
  • NC_000013.11:g.51941185C>G
  • NG_008806.1:g.75310G>C
  • NM_000053.4:c.3452G>CMANE SELECT
  • NM_001005918.3:c.2831G>C
  • NM_001243182.2:c.3119G>C
  • NM_001330578.2:c.3218G>C
  • NM_001330579.2:c.3200G>C
  • NP_000044.2:p.Arg1151Pro
  • NP_001005918.1:p.Arg944Pro
  • NP_001230111.1:p.Arg1040Pro
  • NP_001317507.1:p.Arg1073Pro
  • NP_001317508.1:p.Arg1067Pro
  • NC_000013.10:g.52515321C>G
Protein change:
R1040P
Links:
dbSNP: rs377297166
NCBI 1000 Genomes Browser:
rs377297166
Molecular consequence:
  • NM_000053.4:c.3452G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001005918.3:c.2831G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001243182.2:c.3119G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330578.2:c.3218G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330579.2:c.3200G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Wilson disease (WND)
Synonyms:
Wilson's disease; Hepatolenticular degeneration
Identifiers:
MONDO: MONDO:0010200; MedGen: C0019202; Orphanet: 905; OMIM: 277900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002506299ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process 2021)		Uncertain significance
(Feb 10, 2022) 		germlineclinical testing

Citation Link,

SCV002779286Fulgent Genetics, Fulgent Genetics
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Apr 11, 2022) 		unknownclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV002506299.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The ATP7B c.3452G>C; p.Arg1151Pro variant (rs377297166), to our knowledge, is not reported in the medical literature or gene specific databases. This variant is only observed on one allele in the Genome Aggregation Database, indicating it is not a common polymorphism. Additionally, another variant at this codon (c.3451C>T, p.Arg1151Cys) has been reported in individuals with Wilson disease and is considered likely pathogenic (Lee 2011, Lepori 2007); however this variant creates a cysteine which are involved in heavy metal binding (Forbes 1999). The arginine at codon 1151 is moderately conserved, and computational analyses predict that this variant is deleterious (REVEL: 0.894). However, given the lack of clinical and functional data, the significance of the p.Arg1151Pro variant is uncertain at this time. References: Forbes JR et al. Role of the copper-binding domain in the copper transport function of ATP7B, the P-type ATPase defective in Wilson disease. J Biol Chem. 1999 Apr 30;274(18):12408-13. PMID: 10212214. Lee BH et al. Distinct clinical courses according to presenting phenotypes and their correlations to ATP7B mutations in a large Wilson's disease cohort. Liver Int. 2011 Jul;31(6):831-9. Liver Int. 2011 Sep;31(8):1242. PMID: 21645214. Lepori MB et al. Twenty-four novel mutations in Wilson disease patients of predominantly Italian origin. Genet Test. 2007 Fall;11(3):328-32. PMID: 17949296.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Fulgent Genetics, Fulgent Genetics, SCV002779286.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Dec 24, 2023