13-51946335-C-T

Position:

chr13-51946335-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000053.4(ATP7B):c.3009G>A(p.Ala1003=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0565 in 1,607,684 control chromosomes in the GnomAD database, including 3,036 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.043 ( 217 hom., cov: 33)

Exomes 𝑓: 0.058 ( 2819 hom. )

Consequence

ATP7B
NM_000053.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:15

Conservation

PhyloP100: -4.22

Variant links:

Genes affected

ATP7B (HGNC:870): (ATPase copper transporting beta) This gene is a member of the P-type cation transport ATPase family and encodes a protein with several membrane-spanning domains, an ATPase consensus sequence, a hinge domain, a phosphorylation site, and at least 2 putative copper-binding sites. This protein is a monomer, and functions as a copper-transporting ATPase which exports copper out of the cells, such as the efflux of hepatic copper into the bile. Alternate transcriptional splice variants, encoding different isoforms with distinct cellular localizations, have been characterized. Mutations in this gene have been associated with Wilson disease which is characterized by copper accumulation. [provided by RefSeq, Dec 2019]

ATP7B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 13-51946335-C-T is Benign according to our data. Variant chr13-51946335-C-T is described in ClinVar as [Benign]. Clinvar id is 35714.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-51946335-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-4.22 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP7B	NM_000053.4 linkuse as main transcript	c.3009G>A	p.Ala1003=	synonymous_variant	13/21	ENST00000242839.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP7B	ENST00000242839.10 linkuse as main transcript	c.3009G>A	p.Ala1003=	synonymous_variant	13/21	1	NM_000053.4	P1	P35670-1

Frequencies

GnomAD3 genomes

AF:

0.0427

AC:

6500

AN:

152230

Hom.:

213

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00916

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.0316

Gnomad ASJ

AF:

0.0746

Gnomad EAS

AF:

0.0110

Gnomad SAS

AF:

0.113

Gnomad FIN

AF:

0.0764

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0564

Gnomad OTH

AF:

0.0435

GnomAD3 exomes

AF:

0.0549

AC:

13079

AN:

238048

Hom.:

477

AF XY:

0.0609

AC XY:

7879

AN XY:

129412

show subpopulations

Gnomad AFR exome

AF:

0.00674

Gnomad AMR exome

AF:

0.0230

Gnomad ASJ exome

AF:

0.0717

Gnomad EAS exome

AF:

0.00965

Gnomad SAS exome

AF:

0.112

Gnomad FIN exome

AF:

0.0763

Gnomad NFE exome

AF:

0.0572

Gnomad OTH exome

AF:

0.0569

GnomAD4 exome

AF:

0.0580

AC:

84356

AN:

1455336

Hom.:

2819

Cov.:

AF XY:

0.0601

AC XY:

43504

AN XY:

723460

show subpopulations

Gnomad4 AFR exome

AF:

0.00701

Gnomad4 AMR exome

AF:

0.0232

Gnomad4 ASJ exome

AF:

0.0727

Gnomad4 EAS exome

AF:

0.00936

Gnomad4 SAS exome

AF:

0.116

Gnomad4 FIN exome

AF:

0.0765

Gnomad4 NFE exome

AF:

0.0570

Gnomad4 OTH exome

AF:

0.0556

GnomAD4 genome

AF:

0.0427

AC:

6503

AN:

152348

Hom.:

217

Cov.:

AF XY:

0.0441

AC XY:

3287

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00911

Gnomad4 AMR

AF:

0.0315

Gnomad4 ASJ

AF:

0.0746

Gnomad4 EAS

AF:

0.0110

Gnomad4 SAS

AF:

0.113

Gnomad4 FIN

AF:

0.0764

Gnomad4 NFE

AF:

0.0564

Gnomad4 OTH

AF:

0.0477

Alfa

AF:

0.0458

Hom.:

Bravo

AF:

0.0356

Asia WGS

AF:

0.0660

AC:

228

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:15

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 18, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 26, 2013	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Wilson disease

Benign:7

Benign, criteria provided, single submitter	clinical testing;curation	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Aug 18, 2011	- -
Benign, criteria provided, single submitter	clinical testing	All of Us Research Program, National Institutes of Health	Feb 05, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Color Diagnostics, LLC DBA Color Health	Mar 28, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 03, 2016

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

1.6

DANN

Benign

0.54

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over