NM_000053.4(ATP7B):c.3237T>A (p.Cys1079Ter) AND Wilson disease

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Aug 10, 2021
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:: RCV001263752.11

Allele description [Variation Report for NM_000053.4(ATP7B):c.3237T>A (p.Cys1079Ter)]

NM_000053.4(ATP7B):c.3237T>A (p.Cys1079Ter)

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.3237T>A (p.Cys1079Ter)

HGVS:

NC_000013.11:g.51944115A>T
NG_008806.1:g.72380T>A
NM_000053.4:c.3237T>AMANE SELECT
NM_001005918.3:c.2616T>A
NM_001243182.2:c.2904T>A
NM_001330578.2:c.3003T>A
NM_001330579.2:c.2985T>A
NP_000044.2:p.Cys1079Ter
NP_001005918.1:p.Cys872Ter
NP_001230111.1:p.Cys968Ter
NP_001317507.1:p.Cys1001Ter
NP_001317508.1:p.Cys995Ter
NC_000013.10:g.52518251A>T

Protein change:

C1001*

Links:

dbSNP: rs1957506216

NCBI 1000 Genomes Browser:

rs1957506216

Molecular consequence:

NM_000053.4:c.3237T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001005918.3:c.2616T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001243182.2:c.2904T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001330578.2:c.3003T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001330579.2:c.2985T>A - nonsense - [Sequence Ontology: SO:0001587]

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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Salivary Gland Polymorphous Adenocarcinoma

MedGen
C1335907[conceptid] (1)
MedGen
Homo sapiens, Similar to proteasome (prosome, macropain) 26S subunit, non-ATPase...
Homo sapiens, Similar to proteasome (prosome, macropain) 26S subunit, non-ATPase, 1, clone IMAGE:5553838, mRNA, partial cds
gi|24981060|gb|BC039845.1|

Nucleotide
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Homo sapiens proteasome (prosome, macropain) 26S subunit, non-ATPase, 1, mRNA (cDNA clone MGC:104523 IMAGE:4826340), complete cds
gi|63102250|gb|BC094720.1|

Nucleotide
Oropharyngeal Polymorphous Adenocarcinoma
Oropharyngeal Polymorphous Adenocarcinoma

MedGen

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001441845	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Women's Health Autosomal Recessive and X-Linked Classification Criteria (2019))	Likely pathogenic (Nov 4, 2019)	unknown	clinical testing	Citation Link,
SCV001580267	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 29, 2020)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 10441329, 16283883, 28492532
SCV001977264	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 10, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001441845

Myriad Genetics, Inc.

criteria provided, single submitter

(Myriad Women's Health Autosomal Recessive and X-Linked Classification Criteria (2019))

Likely pathogenic
(Nov 4, 2019)

unknown

clinical testing

Citation Link,

SCV001580267

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 29, 2020)

germline

clinical testing

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

SCV001977264

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Aug 10, 2021)

germline

clinical testing

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	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Null mutation of the murine ATP7B (Wilson disease) gene results in intracellular copper accumulation and late-onset hepatic nodular transformation.

Buiakova OI, Xu J, Lutsenko S, Zeitlin S, Das K, Das S, Ross BM, Mekios C, Scheinberg IH, Gilliam TC.

Hum Mol Genet. 1999 Sep;8(9):1665-71.

PubMed [citation]

PMID:: 10441329

Frameshift and nonsense mutations in the gene for ATPase7B are associated with severe impairment of copper metabolism and with an early clinical manifestation of Wilson's disease.

Gromadzka G, Schmidt HH, Genschel J, Bochow B, Rodo M, Tarnacka B, Litwin T, Chabik G, Członkowska A.

Clin Genet. 2005 Dec;68(6):524-32.

PubMed [citation]

PMID:: 16283883

See all PubMed Citations (4)

Details of each submission

From Myriad Genetics, Inc., SCV001441845.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001580267.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Cys1079*) in the ATP7B gene. It is expected to result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in ATP7B are known to be pathogenic (PMID: 10441329, 16283883). This variant has not been reported in the literature in individuals with ATP7B-related conditions. This variant is not present in population databases (ExAC 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

From Genome-Nilou Lab, SCV001977264.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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