chr13-51933371-C-T

Position:

• chr13-51933371-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_000053.4(ATP7B):​c.*1385G>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 0.0099 in 152,220 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0099 (7 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: ATP7B NM_000053.4 3_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: -0.150

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 13-51933371-C-T is Benign according to our data. Variant chr13-51933371-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 312354.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP7B	NM_000053.4	c.*1385G>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.*1385G>A		3_prime_UTR_variant	21/21	1	NM_000053.4	P1

Frequencies

GnomAD3 genomes AF: 0.00990 AC: 1506 AN: 152102 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.00816

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.00871

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0137

Gnomad FIN AF: 0.0224

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00960

Gnomad OTH AF: 0.0148

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.00990 AC: 1507 AN: 152220 Hom.: 7 Cov.: 33 AF XY: 0.0101 AC XY: 749 AN XY: 74432

Gnomad4 AFR AF: 0.00814

Gnomad4 AMR AF: 0.00870

Gnomad4 ASJ AF: 0.0112

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0139

Gnomad4 FIN AF: 0.0224

Gnomad4 NFE AF: 0.00960

Gnomad4 OTH AF: 0.0152

Alfa AF: 0.00891 Hom.: 1

Bravo AF: 0.00922

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Wilson disease Uncertain:1

Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2023

ATP7B: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.4
DANN	Benign	0.44

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: rs41292780; hg19: chr13-52507507;