NM_000053.4(ATP7B):c.1726G>A (p.Ala576Thr) AND Wilson disease

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jan 25, 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:: RCV001210728.9

Allele description [Variation Report for NM_000053.4(ATP7B):c.1726G>A (p.Ala576Thr)]

NM_000053.4(ATP7B):c.1726G>A (p.Ala576Thr)

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.1726G>A (p.Ala576Thr)

HGVS:

NC_000013.11:g.51965015C>T
NG_008806.1:g.51480G>A
NM_000053.4:c.1726G>AMANE SELECT
NM_001005918.3:c.1726G>A
NM_001243182.2:c.1393G>A
NM_001330578.2:c.1726G>A
NM_001330579.2:c.1726G>A
NP_000044.2:p.Ala576Thr
NP_001005918.1:p.Ala576Thr
NP_001230111.1:p.Ala465Thr
NP_001317507.1:p.Ala576Thr
NP_001317508.1:p.Ala576Thr
NC_000013.10:g.52539151C>T
NM_000053.3:c.1726G>A

Protein change:

A465T

Links:

dbSNP: rs747638528

NCBI 1000 Genomes Browser:

rs747638528

Molecular consequence:

NM_000053.4:c.1726G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001005918.3:c.1726G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001243182.2:c.1393G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001330578.2:c.1726G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001330579.2:c.1726G>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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001382229	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 25, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002087867	Natera, Inc.	no assertion criteria provided	Uncertain significance (Apr 30, 2021)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001382229

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 25, 2022)

germline

clinical testing

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

SCV002087867

Natera, Inc.

no assertion criteria provided

Uncertain significance
(Apr 30, 2021)

germline

clinical testing

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001382229.4

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

Description

This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 576 of the ATP7B protein (p.Ala576Thr). This variant is present in population databases (rs747638528, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with ATP7B-related conditions. ClinVar contains an entry for this variant (Variation ID: 941024). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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

From Natera, Inc., SCV002087867.1

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

#	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

ClinVar

Relating variation to medicine