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NM_000053.4(ATP7B):c.2986A>G (p.Met996Val) AND Wilson disease

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Apr 5, 2022
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:
RCV002996807.3

Allele description [Variation Report for NM_000053.4(ATP7B):c.2986A>G (p.Met996Val)]

NM_000053.4(ATP7B):c.2986A>G (p.Met996Val)

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.2986A>G (p.Met996Val)
HGVS:
  • NC_000013.11:g.51946358T>C
  • NG_008806.1:g.70137A>G
  • NM_000053.4:c.2986A>GMANE SELECT
  • NM_001005918.3:c.2365A>G
  • NM_001243182.2:c.2653A>G
  • NM_001330578.2:c.2752A>G
  • NM_001330579.2:c.2734A>G
  • NM_001406511.1:c.2986A>G
  • NM_001406512.1:c.2986A>G
  • NM_001406513.1:c.2986A>G
  • NM_001406514.1:c.2953A>G
  • NM_001406515.1:c.2932A>G
  • NM_001406516.1:c.2932A>G
  • NM_001406517.1:c.2890A>G
  • NM_001406518.1:c.2890A>G
  • NM_001406519.1:c.2851A>G
  • NM_001406520.1:c.2842A>G
  • NM_001406521.1:c.2842A>G
  • NM_001406522.1:c.2842A>G
  • NM_001406523.1:c.2986A>G
  • NM_001406524.1:c.2809A>G
  • NM_001406526.1:c.2986A>G
  • NM_001406527.1:c.2752A>G
  • NM_001406528.1:c.2752A>G
  • NM_001406530.1:c.2746A>G
  • NM_001406531.1:c.2734A>G
  • NM_001406532.1:c.2734A>G
  • NM_001406534.1:c.2698A>G
  • NM_001406536.1:c.2656A>G
  • NM_001406538.1:c.2752A>G
  • NM_001406539.1:c.2557A>G
  • NM_001406541.1:c.2500A>G
  • NM_001406542.1:c.2500A>G
  • NM_001406543.1:c.2638A>G
  • NM_001406544.1:c.2404A>G
  • NM_001406545.1:c.2338A>G
  • NM_001406548.1:c.1696A>G
  • NP_000044.2:p.Met996Val
  • NP_001005918.1:p.Met789Val
  • NP_001230111.1:p.Met885Val
  • NP_001317507.1:p.Met918Val
  • NP_001317508.1:p.Met912Val
  • NP_001393440.1:p.Met996Val
  • NP_001393441.1:p.Met996Val
  • NP_001393442.1:p.Met996Val
  • NP_001393443.1:p.Met985Val
  • NP_001393444.1:p.Met978Val
  • NP_001393445.1:p.Met978Val
  • NP_001393446.1:p.Met964Val
  • NP_001393447.1:p.Met964Val
  • NP_001393448.1:p.Met951Val
  • NP_001393449.1:p.Met948Val
  • NP_001393450.1:p.Met948Val
  • NP_001393451.1:p.Met948Val
  • NP_001393452.1:p.Met996Val
  • NP_001393453.1:p.Met937Val
  • NP_001393455.1:p.Met996Val
  • NP_001393456.1:p.Met918Val
  • NP_001393457.1:p.Met918Val
  • NP_001393459.1:p.Met916Val
  • NP_001393460.1:p.Met912Val
  • NP_001393461.1:p.Met912Val
  • NP_001393463.1:p.Met900Val
  • NP_001393465.1:p.Met886Val
  • NP_001393467.1:p.Met918Val
  • NP_001393468.1:p.Met853Val
  • NP_001393470.1:p.Met834Val
  • NP_001393471.1:p.Met834Val
  • NP_001393472.1:p.Met880Val
  • NP_001393473.1:p.Met802Val
  • NP_001393474.1:p.Met780Val
  • NP_001393477.1:p.Met566Val
  • NC_000013.10:g.52520494T>C
Protein change:
M566V
Molecular consequence:
  • NM_000053.4:c.2986A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001005918.3:c.2365A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001243182.2:c.2653A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330578.2:c.2752A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330579.2:c.2734A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406511.1:c.2986A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406512.1:c.2986A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406513.1:c.2986A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406514.1:c.2953A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406515.1:c.2932A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406516.1:c.2932A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406517.1:c.2890A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406518.1:c.2890A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406519.1:c.2851A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406520.1:c.2842A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406521.1:c.2842A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406522.1:c.2842A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406523.1:c.2986A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406524.1:c.2809A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406526.1:c.2986A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406527.1:c.2752A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406528.1:c.2752A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406530.1:c.2746A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406531.1:c.2734A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406532.1:c.2734A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406534.1:c.2698A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406536.1:c.2656A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406538.1:c.2752A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406539.1:c.2557A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406541.1:c.2500A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406542.1:c.2500A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406543.1:c.2638A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406544.1:c.2404A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406545.1:c.2338A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406548.1:c.1696A>G - 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
SCV003314850Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Apr 5, 2022) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Twenty-four novel mutations in Wilson disease patients of predominantly European ancestry.

Cox DW, Prat L, Walshe JM, Heathcote J, Gaffney D.

Hum Mutat. 2005 Sep;26(3):280.

PubMed [citation]
PMID:
16088907

Molecular analysis of Wilson patients: direct sequencing and MLPA analysis in the ATP7B gene and Atox1 and COMMD1 gene analysis.

Bost M, Piguet-Lacroix G, Parant F, Wilson CM.

J Trace Elem Med Biol. 2012 Jun;26(2-3):97-101. doi: 10.1016/j.jtemb.2012.04.024. Epub 2012 Jun 5.

PubMed [citation]
PMID:
22677543
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003314850.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Met996 amino acid residue in ATP7B. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16088907, 22677543; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ATP7B protein function. This variant has not been reported in the literature in individuals affected with ATP7B-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 996 of the ATP7B protein (p.Met996Val).

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

Last Updated: Sep 29, 2024