NM_000053.4(ATP7B):c.1171T>C (p.Ser391Pro) AND Wilson disease

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 18, 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:: RCV003077880.4

Allele description [Variation Report for NM_000053.4(ATP7B):c.1171T>C (p.Ser391Pro)]

NM_000053.4(ATP7B):c.1171T>C (p.Ser391Pro)

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.1171T>C (p.Ser391Pro)

HGVS:

NC_000013.11:g.51974049A>G
NG_008806.1:g.42446T>C
NM_000053.4:c.1171T>CMANE SELECT
NM_001005918.3:c.1171T>C
NM_001243182.2:c.838T>C
NM_001330578.2:c.1171T>C
NM_001330579.2:c.1171T>C
NM_001406511.1:c.1171T>C
NM_001406512.1:c.1171T>C
NM_001406513.1:c.1171T>C
NM_001406514.1:c.1171T>C
NM_001406515.1:c.1171T>C
NM_001406516.1:c.1171T>C
NM_001406517.1:c.1075T>C
NM_001406518.1:c.1075T>C
NM_001406519.1:c.1171T>C
NM_001406520.1:c.1171T>C
NM_001406521.1:c.1171T>C
NM_001406522.1:c.1171T>C
NM_001406523.1:c.1171T>C
NM_001406524.1:c.1171T>C
NM_001406525.1:c.1171T>C
NM_001406526.1:c.1171T>C
NM_001406527.1:c.1171T>C
NM_001406528.1:c.1171T>C
NM_001406530.1:c.1075T>C
NM_001406531.1:c.1171T>C
NM_001406532.1:c.1171T>C
NM_001406534.1:c.1171T>C
NM_001406535.1:c.1171T>C
NM_001406536.1:c.1075T>C
NM_001406537.1:c.1171T>C
NM_001406538.1:c.1171T>C
NM_001406539.1:c.742T>C
NM_001406540.1:c.1171T>C
NM_001406541.1:c.1171T>C
NM_001406542.1:c.1171T>C
NM_001406543.1:c.1075T>C
NM_001406544.1:c.1075T>C
NM_001406545.1:c.1171T>C
NM_001406546.1:c.1171T>C
NM_001406547.1:c.1171T>C
NM_001406548.1:c.1171T>C
NP_000044.2:p.Ser391Pro
NP_001005918.1:p.Ser391Pro
NP_001230111.1:p.Ser280Pro
NP_001317507.1:p.Ser391Pro
NP_001317508.1:p.Ser391Pro
NP_001393440.1:p.Ser391Pro
NP_001393441.1:p.Ser391Pro
NP_001393442.1:p.Ser391Pro
NP_001393443.1:p.Ser391Pro
NP_001393444.1:p.Ser391Pro
NP_001393445.1:p.Ser391Pro
NP_001393446.1:p.Ser359Pro
NP_001393447.1:p.Ser359Pro
NP_001393448.1:p.Ser391Pro
NP_001393449.1:p.Ser391Pro
NP_001393450.1:p.Ser391Pro
NP_001393451.1:p.Ser391Pro
NP_001393452.1:p.Ser391Pro
NP_001393453.1:p.Ser391Pro
NP_001393454.1:p.Ser391Pro
NP_001393455.1:p.Ser391Pro
NP_001393456.1:p.Ser391Pro
NP_001393457.1:p.Ser391Pro
NP_001393459.1:p.Ser359Pro
NP_001393460.1:p.Ser391Pro
NP_001393461.1:p.Ser391Pro
NP_001393463.1:p.Ser391Pro
NP_001393464.1:p.Ser391Pro
NP_001393465.1:p.Ser359Pro
NP_001393466.1:p.Ser391Pro
NP_001393467.1:p.Ser391Pro
NP_001393468.1:p.Ser248Pro
NP_001393469.1:p.Ser391Pro
NP_001393470.1:p.Ser391Pro
NP_001393471.1:p.Ser391Pro
NP_001393472.1:p.Ser359Pro
NP_001393473.1:p.Ser359Pro
NP_001393474.1:p.Ser391Pro
NP_001393475.1:p.Ser391Pro
NP_001393476.1:p.Ser391Pro
NP_001393477.1:p.Ser391Pro
NC_000013.10:g.52548185A>G

Protein change:

S248P

Molecular consequence:

NM_000053.4:c.1171T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001005918.3:c.1171T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001243182.2:c.838T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001330578.2:c.1171T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001330579.2:c.1171T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406511.1:c.1171T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406512.1:c.1171T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406513.1:c.1171T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406514.1:c.1171T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406515.1:c.1171T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406516.1:c.1171T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406517.1:c.1075T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406518.1:c.1075T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406519.1:c.1171T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406520.1:c.1171T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406521.1:c.1171T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406522.1:c.1171T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406523.1:c.1171T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406524.1:c.1171T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406525.1:c.1171T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406526.1:c.1171T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406527.1:c.1171T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406528.1:c.1171T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406530.1:c.1075T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406531.1:c.1171T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406532.1:c.1171T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406534.1:c.1171T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406535.1:c.1171T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406536.1:c.1075T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406537.1:c.1171T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406538.1:c.1171T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406539.1:c.742T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406540.1:c.1171T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406541.1:c.1171T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406542.1:c.1171T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406543.1:c.1075T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406544.1:c.1075T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406545.1:c.1171T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406546.1:c.1171T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406547.1:c.1171T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406548.1:c.1171T>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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
SCV003468609	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 22, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004817200	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Dec 18, 2023)	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

SCV003468609

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 22, 2022)

germline

clinical testing

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

SCV004817200

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(Dec 18, 2023)

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	unknown	4	not provided	not provided	108544	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

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV003468609.1

#	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 serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 391 of the ATP7B protein (p.Ser391Pro). This variant is present in population databases (rs755785474, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with ATP7B-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ATP7B 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 All of Us Research Program, National Institutes of Health, SCV004817200.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	4	not provided	not provided	clinical testing	PubMed (1)

Description

This missense variant replaces serine with proline at codon 391 of the ATP7B protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with ATP7B-related disorders in the literature. This variant has been identified in 1/249546 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is 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	108544	not provided	not provided		4	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine