rs1051332

chr13-51933584-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000053.4(ATP7B):c.*1172G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 152,128 control chromosomes in the GnomAD database, including 11,325 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.36 (11321 hom., cov: 32)
  • Exomes 𝑓: 0.56 (4 hom.)
• Consequence: ATP7B NM_000053.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.36

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]

TMEM272 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 13-51933584-C-T is Benign according to our data. Variant chr13-51933584-C-T is described in ClinVar as [Benign]. Clinvar id is 312357.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP7B	NM_000053.4	c.*1172G>A		3_prime_UTR_variant	21/21	ENST00000242839.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP7B	ENST00000242839.10	c.*1172G>A		3_prime_UTR_variant	21/21	1	NM_000053.4	P1

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54127 AN: 151992 Hom.: 11325 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.416

GnomAD4 exome AF: 0.556 AC: 10 AN: 18 Hom.: 4 Cov.: 0 AF XY: 0.429 AC XY: 6 AN XY: 14

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.700

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.356 AC: 54121 AN: 152110 Hom.: 11321 Cov.: 32 AF XY: 0.357 AC XY: 26532 AN XY: 74340

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.376

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.357

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.473

Gnomad4 NFE AF: 0.472

Gnomad4 OTH AF: 0.414

Alfa AF: 0.445 Hom.: 21795

Bravo AF: 0.342

Asia WGS AF: 0.363 AC: 1258 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Wilson disease Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.50
Dann	Benign	0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1051332; hg19: chr13-52507720; COSMIC: COSV54444834; COSMIC: COSV54444834;