13-51933012-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000053.4(ATP7B):c.*1744C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0334 in 152,160 control chromosomes in the GnomAD database, including 138 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.033 (138 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ATP7B NM_000053.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.168

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=-0.87).
• BP6: Variant 13-51933012-G-A is Benign according to our data. Variant chr13-51933012-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 881669.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0334 (5081/152160) while in subpopulation SAS AF= 0.0511 (246/4818). AF 95% confidence interval is 0.0458. There are 138 homozygotes in gnomad4. There are 2533 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 138 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP7B	NM_000053.4	c.*1744C>T		3_prime_UTR_variant	21/21	ENST00000242839.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP7B	ENST00000242839.10	c.*1744C>T		3_prime_UTR_variant	21/21	1	NM_000053.4	P1

Frequencies

GnomAD3 genomes AF: 0.0335 AC: 5087 AN: 152042 Hom.: 138 Cov.: 33

Gnomad AFR AF: 0.00660

Gnomad AMI AF: 0.0187

Gnomad AMR AF: 0.0269

Gnomad ASJ AF: 0.0709

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0514

Gnomad FIN AF: 0.0688

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0452

Gnomad OTH AF: 0.0349

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0334 AC: 5081 AN: 152160 Hom.: 138 Cov.: 33 AF XY: 0.0341 AC XY: 2533 AN XY: 74388

Gnomad4 AFR AF: 0.00655

Gnomad4 AMR AF: 0.0268

Gnomad4 ASJ AF: 0.0709

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0511

Gnomad4 FIN AF: 0.0688

Gnomad4 NFE AF: 0.0452

Gnomad4 OTH AF: 0.0341

Alfa AF: 0.0387 Hom.: 158

Bravo AF: 0.0282

Asia WGS AF: 0.0200 AC: 70 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Wilson disease Benign:1

Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.92
Dann	Benign	0.66

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: rs9535794; hg19: chr13-52507148; COSMIC: COSV54442930; COSMIC: COSV54442930;