rs587783319

Positions:

• chr13-52011297-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The ENST00000242839.10(ATP7B):​c.41C>A​(p.Ala14Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A14T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: ATP7B ENST00000242839.10 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.24

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12293866).
• BP6: Variant 13-52011297-G-T is Benign according to our data. Variant chr13-52011297-G-T is described in ClinVar as [Benign]. Clinvar id is 157958.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP7B	NM_000053.4	c.41C>A	p.Ala14Asp	missense_variant	1/21	ENST00000242839.10	NP_000044.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP7B	ENST00000242839.10	c.41C>A	p.Ala14Asp	missense_variant	1/21	1	NM_000053.4	ENSP00000242839	P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 34

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Feb 08, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Benign	19
DANN	Benign	0.93
DEOGEN2	Benign	0.41	T;T;.;.;.;.;.
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.31	T;T;T;T;T;T;T
M_CAP	Uncertain	0.091	D
MetaRNN	Benign	0.12	T;T;T;T;T;T;T
MetaSVM	Uncertain	0.25	D
MutationAssessor	Benign	1.4	L;.;L;L;.;.;.
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.94	N;N;N;N;N;.;N
REVEL	Uncertain	0.29
Sift	Uncertain	0.027	D;D;D;D;T;.;D
Sift4G	Benign	0.30	T;T;T;T;T;T;T
Polyphen		0.073	B;P;P;P;P;B;B
Vest4		0.47
MutPred		0.11		Loss of MoRF binding (P = 0.0433);Loss of MoRF binding (P = 0.0433);Loss of MoRF binding (P = 0.0433);Loss of MoRF binding (P = 0.0433);Loss of MoRF binding (P = 0.0433);Loss of MoRF binding (P = 0.0433);Loss of MoRF binding (P = 0.0433);
MVP		0.94
MPC		0.085
ClinPred		0.070	T
GERP RS		2.1
Varity_R		0.12
gMVP		0.36

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

Other links and lift over

dbSNP: rs587783319; hg19: chr13-52585433;