rs587783314

Variant names:

• chr13-51941139-A-C
• NM_000053.4:c.3498T>G

Your query was ambiguous. Multiple possible variants found:

• chr13-51941139-A-C
• chr13-51941139-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000053.4(ATP7B):​c.3498T>G​(p.Ser1166Arg) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ATP7B NM_000053.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.224

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16235578).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP7B	NM_000053.4	c.3498T>G	p.Ser1166Arg	missense_variant	Exon 16 of 21	ENST00000242839.10	NP_000044.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP7B	ENST00000242839.10	c.3498T>G	p.Ser1166Arg	missense_variant	Exon 16 of 21	1	NM_000053.4	ENSP00000242839.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	11
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.75	D;D;.;.;.;.;.
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.56
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.80	T;T;T;T;T;T;T
M_CAP	Pathogenic	0.39	D
MetaRNN	Benign	0.16	T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Benign	0.13	N;.;.;.;.;.;.
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-2.0	N;N;N;N;N;.;N
REVEL	Uncertain	0.39
Sift	Benign	0.062	T;D;T;T;T;.;T
Sift4G	Benign	0.13	T;T;T;T;D;T;T
Polyphen		0.0030	B;B;B;B;B;B;B
Vest4		0.23
MutPred		0.36		Loss of catalytic residue at S1163 (P = 0.0506);.;.;.;.;.;.;
MVP		0.90
MPC		0.18
ClinPred		0.80	D
GERP RS		-2.2
Varity_R		0.24
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-52515275;