rs138427376

Positions:

• chr13-51968544-A-C
• chr13-51968544-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000053.4(ATP7B):​c.1607T>G​(p.Val536Gly) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V536A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATP7B NM_000053.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.321877).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP7B	NM_000053.4	c.1607T>G	p.Val536Gly	missense_variant	4/21	ENST00000242839.10	NP_000044.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP7B	ENST00000242839.10	c.1607T>G	p.Val536Gly	missense_variant	4/21	1	NM_000053.4	ENSP00000242839.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.80	D;D;.;.;.;.
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.78	T;T;T;T;T;T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.32	T;T;T;T;T;T
MetaSVM	Uncertain	-0.075	T
MutationAssessor	Benign	1.9	M;.;M;.;.;.
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-3.7	D;D;D;D;.;D
REVEL	Uncertain	0.32
Sift	Benign	0.036	D;T;D;D;.;D
Sift4G	Benign	0.10	T;T;T;T;T;T
Polyphen		0.18	B;B;B;P;P;P
Vest4		0.27
MutPred		0.67		Loss of stability (P = 0.0118);Loss of stability (P = 0.0118);Loss of stability (P = 0.0118);.;Loss of stability (P = 0.0118);Loss of stability (P = 0.0118);
MVP		0.92
MPC		0.12
ClinPred		0.31	T
GERP RS		1.7
Varity_R		0.38
gMVP		0.46

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: rs138427376; hg19: chr13-52542680;