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NM_000053.4(ATP7B):c.1142T>G (p.Ile381Ser) AND not specified

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Aug 30, 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:
RCV003331123.1

Allele description [Variation Report for NM_000053.4(ATP7B):c.1142T>G (p.Ile381Ser)]

NM_000053.4(ATP7B):c.1142T>G (p.Ile381Ser)

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.1142T>G (p.Ile381Ser)
HGVS:
  • NC_000013.11:g.51974078A>C
  • NG_008806.1:g.42417T>G
  • NM_000053.4:c.1142T>GMANE SELECT
  • NM_001005918.3:c.1142T>G
  • NM_001243182.2:c.809T>G
  • NM_001330578.2:c.1142T>G
  • NM_001330579.2:c.1142T>G
  • NP_000044.2:p.Ile381Ser
  • NP_001005918.1:p.Ile381Ser
  • NP_001230111.1:p.Ile270Ser
  • NP_001317507.1:p.Ile381Ser
  • NP_001317508.1:p.Ile381Ser
  • NC_000013.10:g.52548214A>C
  • NM_000053.3:c.1142T>G
Protein change:
I270S
Links:
dbSNP: rs766943890
NCBI 1000 Genomes Browser:
rs766943890
Molecular consequence:
  • NM_000053.4:c.1142T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001005918.3:c.1142T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001243182.2:c.809T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330578.2:c.1142T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330579.2:c.1142T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV004037737Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)
Uncertain significance
(Aug 30, 2023)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

ATP7B Genotype and Chronic Liver Disease Treatment Outcomes in Wilson Disease: Worse Survival With Loss-of-Function Variants.

Nayagam JS, Jeyaraj R, Foskett P, Dhawan A, Ala A, Joshi D, Bomford A, Thompson RJ.

Clin Gastroenterol Hepatol. 2023 May;21(5):1323-1329.e4. doi: 10.1016/j.cgh.2022.08.041. Epub 2022 Sep 9.

PubMed [citation]
PMID:
36096368

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004037737.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

Variant summary: ATP7B c.1142T>G (p.Ile381Ser) results in a non-conservative amino acid change located in the Heavy metal-associated domain, HMA (IPR006121) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 249546 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1142T>G has been reported in the literature in individuals affected with Wilson Disease without strong evidence of causality (Coffey_2013, Nagayam_2023), and in one patient the variant was found in cis with another missense variant. These reports do not provide unequivocal conclusions about association of the variant with Wilson Disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 23518715, 36096368). One submitter has cited a clinical-significance assessment for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024