13-51932974-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000053.4(ATP7B):c.*1782C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 151,832 control chromosomes in the GnomAD database, including 23,302 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (23299 hom., cov: 31)
  • Exomes 𝑓: 0.64 (3 hom.)
• Consequence: ATP7B NM_000053.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.671

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 13-51932974-G-C is Benign according to our data. Variant chr13-51932974-G-C is described in ClinVar as [Benign]. Clinvar id is 312343.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP7B	NM_000053.4	c.*1782C>G		3_prime_UTR_variant	21/21	ENST00000242839.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP7B	ENST00000242839.10	c.*1782C>G		3_prime_UTR_variant	21/21	1	NM_000053.4	P1

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83771 AN: 151700 Hom.: 23291 Cov.: 31

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.568

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.578

GnomAD4 exome AF: 0.643 AC: 9 AN: 14 Hom.: 3 Cov.: 0 AF XY: 0.700 AC XY: 7 AN XY: 10

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.700

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.552 AC: 83824 AN: 151818 Hom.: 23299 Cov.: 31 AF XY: 0.552 AC XY: 40955 AN XY: 74158

Gnomad4 AFR AF: 0.494

Gnomad4 AMR AF: 0.588

Gnomad4 ASJ AF: 0.568

Gnomad4 EAS AF: 0.407

Gnomad4 SAS AF: 0.532

Gnomad4 FIN AF: 0.601

Gnomad4 NFE AF: 0.584

Gnomad4 OTH AF: 0.580

Alfa AF: 0.436 Hom.: 1205

Bravo AF: 0.550

Asia WGS AF: 0.527 AC: 1830 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Wilson disease Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.1
Dann	Benign	0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.97

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs928169; hg19: chr13-52507110; COSMIC: COSV54442923; COSMIC: COSV54442923;