NM_000053.4(ATP7B):c.1063C>T (p.Gln355Ter) AND Wilson disease

Germline classification:: Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:: May 16, 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:: RCV000673196.14

Allele description [Variation Report for NM_000053.4(ATP7B):c.1063C>T (p.Gln355Ter)]

NM_000053.4(ATP7B):c.1063C>T (p.Gln355Ter)

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.1063C>T (p.Gln355Ter)

HGVS:

NC_000013.11:g.51974157G>A
NG_008806.1:g.42338C>T
NM_000053.4:c.1063C>TMANE SELECT
NM_001005918.3:c.1063C>T
NM_001243182.2:c.803-73C>T
NM_001330578.2:c.1063C>T
NM_001330579.2:c.1063C>T
NP_000044.2:p.Gln355Ter
NP_001005918.1:p.Gln355Ter
NP_001317507.1:p.Gln355Ter
NP_001317508.1:p.Gln355Ter
NC_000013.10:g.52548293G>A
NM_000053.3:c.1063C>T

Protein change:

Q355*

Links:

dbSNP: rs778490238

NCBI 1000 Genomes Browser:

rs778490238

Molecular consequence:

NM_001243182.2:c.803-73C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_000053.4:c.1063C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001005918.3:c.1063C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001330578.2:c.1063C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001330579.2:c.1063C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000798372	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Likely pathogenic (Mar 7, 2018)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 16283883, 22677543 Citation Link,
SCV001414451	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 27, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 2677543, 30230192, 10441329, 16283883, 28492532
SCV001977386	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]
SCV004827563	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 16, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16283883, 22677543, 25741868

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	1	not provided	not provided	108544	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

[Evaluation of the insulin requirements with an artificial pancreas in the pregnant woman with gestational insulin-dependent diabetes (type I)].

Fernández I, Gutiérrez A, Rodríguez MA, Costa CJ, Sánchez Ramos J, Durán García S.

Med Clin (Barc). 1989 Jun 17;93(3):88-92. Spanish.

PubMed [citation]

PMID:: 2677543

Whole-exome sequencing identifies novel pathogenic variants across the ATP7B gene and some modifiers of Wilson's disease phenotype.

Kluska A, Kulecka M, Litwin T, Dziezyc K, Balabas A, Piatkowska M, Paziewska A, Dabrowska M, Mikula M, Kaminska D, Wiernicka A, Socha P, Czlonkowska A, Ostrowski J.

Liver Int. 2019 Jan;39(1):177-186. doi: 10.1111/liv.13967. Epub 2018 Oct 8.

PubMed [citation]

PMID:: 30230192

See all PubMed Citations (7)

Details of each submission

From Counsyl, SCV000798372.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

#	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, SCV001414451.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 557104). This premature translational stop signal has been observed in individual(s) with Wilson disease (PMID: 2677543, 16283883, 30230192). This variant is present in population databases (rs778490238, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Gln355*) in the ATP7B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATP7B are known to be pathogenic (PMID: 10441329, 16283883).

#	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, SCV001977386.1

#	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

From All of Us Research Program, National Institutes of Health, SCV004827563.1

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

Description

This variant changes 1 nucleotide in exon 2 of the ATP7B gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in two individuals affected with Wilson disease in the literature (PMID: 16283883, 22677543). This variant has been identified in 1/249440 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of ATP7B function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	108544	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Oct 8, 2024

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