13-51974889-G-C

Variant names:

• chr13-51974889-G-C
• NM_000053.4:c.331C>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.331C>G​(p.Gln111Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict 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: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ATP7B NM_000053.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.33

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=0.14292824).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP7B	NM_000053.4	c.331C>G	p.Gln111Glu	missense_variant	Exon 2 of 21	ENST00000242839.10	NP_000044.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP7B	ENST00000242839.10	c.331C>G	p.Gln111Glu	missense_variant	Exon 2 of 21	1	NM_000053.4	ENSP00000242839.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461888 Hom.: 0 Cov.: 34 AF XY: 0.00000413 AC XY: 3 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	17
DANN	Benign	0.51
DEOGEN2	Benign	0.34	T;T;.;.;.;.;.
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.82	T;T;T;T;T;T;T
M_CAP	Benign	0.081	D
MetaRNN	Benign	0.14	T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.10	T
MutationAssessor	Benign	-0.015	N;.;N;N;.;.;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.92	N;N;N;N;N;.;N
REVEL	Benign	0.25
Sift	Benign	0.12	T;T;T;T;T;.;T
Sift4G	Benign	0.60	T;T;T;T;T;T;T
Polyphen		0.11	B;B;P;B;P;B;B
Vest4		0.18
MutPred		0.53		Gain of catalytic residue at Q111 (P = 0.1202);Gain of catalytic residue at Q111 (P = 0.1202);Gain of catalytic residue at Q111 (P = 0.1202);Gain of catalytic residue at Q111 (P = 0.1202);Gain of catalytic residue at Q111 (P = 0.1202);Gain of catalytic residue at Q111 (P = 0.1202);Gain of catalytic residue at Q111 (P = 0.1202);
MVP		0.88
MPC		0.067
ClinPred		0.18	T
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.087
gMVP		0.33

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-52549025;