NM_000053.4(ATP7B):c.3053C>A (p.Ala1018Glu) AND Wilson disease

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 17, 2023
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:: RCV003002678.3

Allele description [Variation Report for NM_000053.4(ATP7B):c.3053C>A (p.Ala1018Glu)]

NM_000053.4(ATP7B):c.3053C>A (p.Ala1018Glu)

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.3053C>A (p.Ala1018Glu)

HGVS:

NC_000013.11:g.51946291G>T
NG_008806.1:g.70204C>A
NM_000053.4:c.3053C>AMANE SELECT
NM_001005918.3:c.2432C>A
NM_001243182.2:c.2720C>A
NM_001330578.2:c.2819C>A
NM_001330579.2:c.2801C>A
NM_001406511.1:c.3053C>A
NM_001406512.1:c.3053C>A
NM_001406513.1:c.3053C>A
NM_001406514.1:c.3020C>A
NM_001406515.1:c.2999C>A
NM_001406516.1:c.2999C>A
NM_001406517.1:c.2957C>A
NM_001406518.1:c.2957C>A
NM_001406519.1:c.2918C>A
NM_001406520.1:c.2909C>A
NM_001406521.1:c.2909C>A
NM_001406522.1:c.2909C>A
NM_001406523.1:c.3053C>A
NM_001406524.1:c.2876C>A
NM_001406526.1:c.3053C>A
NM_001406527.1:c.2819C>A
NM_001406528.1:c.2819C>A
NM_001406530.1:c.2813C>A
NM_001406531.1:c.2801C>A
NM_001406532.1:c.2801C>A
NM_001406534.1:c.2765C>A
NM_001406536.1:c.2723C>A
NM_001406538.1:c.2819C>A
NM_001406539.1:c.2624C>A
NM_001406541.1:c.2567C>A
NM_001406542.1:c.2567C>A
NM_001406543.1:c.2705C>A
NM_001406544.1:c.2471C>A
NM_001406545.1:c.2405C>A
NM_001406548.1:c.1763C>A
NP_000044.2:p.Ala1018Glu
NP_001005918.1:p.Ala811Glu
NP_001230111.1:p.Ala907Glu
NP_001317507.1:p.Ala940Glu
NP_001317508.1:p.Ala934Glu
NP_001393440.1:p.Ala1018Glu
NP_001393441.1:p.Ala1018Glu
NP_001393442.1:p.Ala1018Glu
NP_001393443.1:p.Ala1007Glu
NP_001393444.1:p.Ala1000Glu
NP_001393445.1:p.Ala1000Glu
NP_001393446.1:p.Ala986Glu
NP_001393447.1:p.Ala986Glu
NP_001393448.1:p.Ala973Glu
NP_001393449.1:p.Ala970Glu
NP_001393450.1:p.Ala970Glu
NP_001393451.1:p.Ala970Glu
NP_001393452.1:p.Ala1018Glu
NP_001393453.1:p.Ala959Glu
NP_001393455.1:p.Ala1018Glu
NP_001393456.1:p.Ala940Glu
NP_001393457.1:p.Ala940Glu
NP_001393459.1:p.Ala938Glu
NP_001393460.1:p.Ala934Glu
NP_001393461.1:p.Ala934Glu
NP_001393463.1:p.Ala922Glu
NP_001393465.1:p.Ala908Glu
NP_001393467.1:p.Ala940Glu
NP_001393468.1:p.Ala875Glu
NP_001393470.1:p.Ala856Glu
NP_001393471.1:p.Ala856Glu
NP_001393472.1:p.Ala902Glu
NP_001393473.1:p.Ala824Glu
NP_001393474.1:p.Ala802Glu
NP_001393477.1:p.Ala588Glu
NC_000013.10:g.52520427G>T

Protein change:

A1000E

Molecular consequence:

NM_000053.4:c.3053C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001005918.3:c.2432C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001243182.2:c.2720C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001330578.2:c.2819C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001330579.2:c.2801C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406511.1:c.3053C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406512.1:c.3053C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406513.1:c.3053C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406514.1:c.3020C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406515.1:c.2999C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406516.1:c.2999C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406517.1:c.2957C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406518.1:c.2957C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406519.1:c.2918C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406520.1:c.2909C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406521.1:c.2909C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406522.1:c.2909C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406523.1:c.3053C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406524.1:c.2876C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406526.1:c.3053C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406527.1:c.2819C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406528.1:c.2819C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406530.1:c.2813C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406531.1:c.2801C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406532.1:c.2801C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406534.1:c.2765C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406536.1:c.2723C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406538.1:c.2819C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406539.1:c.2624C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406541.1:c.2567C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406542.1:c.2567C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406543.1:c.2705C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406544.1:c.2471C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406545.1:c.2405C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406548.1:c.1763C>A - 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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CUBN cubilin [Homo sapiens]
Gene ID:8029

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003299796	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jan 17, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 17154398, 30884209, 31059521, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003299796

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jan 17, 2023)

germline

clinical testing

PubMed (4)
[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

Citations

PubMed

Revised King's College score for liver transplantation in adult patients with Wilson's disease.

Petrasek J, Jirsa M, Sperl J, Kozak L, Taimr P, Spicak J, Filip K, Trunecka P.

Liver Transpl. 2007 Jan;13(1):55-61.

PubMed [citation]

PMID:: 17154398

Novel mutations found in the ATP7B gene in Chinese patients with Wilson's disease.

Qian Z, Cui X, Huang Y, Liu Y, Li N, Zheng S, Jiang J, Cui S.

Mol Genet Genomic Med. 2019 May;7(5):e649. doi: 10.1002/mgg3.649. Epub 2019 Mar 18.

PubMed [citation]

PMID:: 30884209
PMCID:: PMC6503029

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003299796.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces alanine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 1018 of the ATP7B protein (p.Ala1018Glu). 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.Ala1018 amino acid residue in ATP7B. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17154398, 30884209, 31059521; 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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).

#	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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