NM_000053.4(ATP7B):c.1728G>A (p.Ala576=) AND not provided

Germline classification:: Benign/Likely benign (4 submissions)
Last evaluated:: Mar 1, 2023
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:: RCV000587027.15

Allele description [Variation Report for NM_000053.4(ATP7B):c.1728G>A (p.Ala576=)]

NM_000053.4(ATP7B):c.1728G>A (p.Ala576=)

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.1728G>A (p.Ala576=)

HGVS:

NC_000013.11:g.51965013C>T
NG_008806.1:g.51482G>A
NM_000053.4:c.1728G>AMANE SELECT
NM_001005918.3:c.1728G>A
NM_001243182.2:c.1395G>A
NM_001330578.2:c.1728G>A
NM_001330579.2:c.1728G>A
NP_000044.2:p.Ala576=
NP_001005918.1:p.Ala576=
NP_001230111.1:p.Ala465=
NP_001317507.1:p.Ala576=
NP_001317508.1:p.Ala576=
NC_000013.10:g.52539149C>T
NM_000053.2:c.1728G>A
NM_000053.3:c.1728G>A

Links:

dbSNP: rs116703544

NCBI 1000 Genomes Browser:

rs116703544

Molecular consequence:

NM_000053.4:c.1728G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001005918.3:c.1728G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001243182.2:c.1395G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001330578.2:c.1728G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001330579.2:c.1728G>A - synonymous variant - [Sequence Ontology: SO:0001819]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000694404	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Benign (Oct 27, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] LabCorp Variant Classification Summary - May 2015.docx, Citation Link,
SCV001807186	Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus	no assertion criteria provided	Likely benign	germline	clinical testing
SCV004133158	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Benign (Mar 1, 2023)	germline	clinical testing	Citation Link,
SCV005215659	Breakthrough Genomics, Breakthrough Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign	germline	not provided	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing, not provided
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A genetic study of Wilson's disease in the United Kingdom.

Coffey AJ, Durkie M, Hague S, McLay K, Emmerson J, Lo C, Klaffke S, Joyce CJ, Dhawan A, Hadzic N, Mieli-Vergani G, Kirk R, Elizabeth Allen K, Nicholl D, Wong S, Griffiths W, Smithson S, Giffin N, Taha A, Connolly S, Gillett GT, Tanner S, et al.

Brain. 2013 May;136(Pt 5):1476-87. doi: 10.1093/brain/awt035. Epub 2013 Mar 21.

PubMed [citation]

PMID:: 23518715
PMCID:: PMC3634195

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 Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000694404.1

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

Description

Variant summary: The ATP7B c.1728G>A (p.Ala576Ala) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect multiple ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 186/122606 control chromosomes (3 homozygotes), predominantly observed in the African subpopulation at a frequency of 0.0161224 (158/9800). This frequency is about 3 times the estimated maximal expected allele frequency of a pathogenic ATP7B variant (0.0054006). In addition, three homozygotes were found in the African subpopulation in controls. These data suggest the variant of interest is a benign polymorphism found primarily in the populations of African origin. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Based on the splicing prediction and allele frequency in controls, this variant is classified as 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

From Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus, SCV001807186.1

#	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	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From CeGaT Center for Human Genetics Tuebingen, SCV004133158.10

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

Description

ATP7B: BP4, BP7, BS1, BS2

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From Breakthrough Genomics, Breakthrough Genomics, SCV005215659.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 20, 2024

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