rs9535794

Variant names:

• chr13-51933012-G-A
• rs9535794
• NM_000053.4:c.*1744C>T

Your query was ambiguous. Multiple possible variants found:

• chr13-51933012-G-A
• chr13-51933012-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.168
• Publications: 6 publications found

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:26737): (transmembrane protein 272) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 881669.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 138 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000053.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP7B	NM_000053.4	MANE Select	c.*1744C>T		3_prime_UTR	Exon 21 of 21	NP_000044.2	P35670-1
	ATP7B	NM_001406511.1		c.*1744C>T		3_prime_UTR	Exon 22 of 22	NP_001393440.1	P35670-1
	ATP7B	NM_001406512.1		c.*1744C>T		3_prime_UTR	Exon 22 of 22	NP_001393441.1	P35670-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP7B	ENST00000242839.10	TSL:1 MANE Select	c.*1744C>T		3_prime_UTR	Exon 21 of 21	ENSP00000242839.5	P35670-1
	ATP7B	ENST00000448424.7	TSL:1	c.*1744C>T		3_prime_UTR	Exon 19 of 19	ENSP00000416738.3	E7ET55
	ATP7B	ENST00000634810.1	TSL:1	n.5487C>T		non_coding_transcript_exon	Exon 14 of 14

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.00655 AC: 272 AN: 41510

American (AMR) AF: 0.0268 AC: 409 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0709 AC: 246 AN: 3468

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5176

South Asian (SAS) AF: 0.0511 AC: 246 AN: 4818

European-Finnish (FIN) AF: 0.0688 AC: 728 AN: 10574

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0452 AC: 3073 AN: 68012

Other (OTH) AF: 0.0341 AC: 72 AN: 2112

Alfa AF: 0.0374 Hom.: 180

Bravo AF: 0.0282

Asia WGS AF: 0.0200 AC: 70 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Wilson disease (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.92
DANN	Benign	0.66
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

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