NM_000053.4:c.1544-53A>T

Variant names:

• chr13-51968660-T-A
• rs2147363
• NM_000053.4:c.1544-53A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000053.4(ATP7B):​c.1544-53A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,940 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ATP7B NM_000053.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 20 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]

ATP7B Gene-Disease associations (from GenCC):

• Wilson disease

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP7B	NM_000053.4	c.1544-53A>T		intron_variant	Intron 3 of 20	ENST00000242839.10	NP_000044.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP7B	ENST00000242839.10	c.1544-53A>T		intron_variant	Intron 3 of 20	1	NM_000053.4	ENSP00000242839.5

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151822 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000138 AC: 2 AN: 1447772 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 721180

African (AFR) AF: 0.00 AC: 0 AN: 33168

American (AMR) AF: 0.00 AC: 0 AN: 44632

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26056

East Asian (EAS) AF: 0.00 AC: 0 AN: 39626

South Asian (SAS) AF: 0.00 AC: 0 AN: 85792

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53118

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4816

European-Non Finnish (NFE) AF: 0.00000182 AC: 2 AN: 1100700

Other (OTH) AF: 0.00 AC: 0 AN: 59864

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151940 Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 1 AN XY: 74222

African (AFR) AF: 0.0000241 AC: 1 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5124

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10550

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67932

Other (OTH) AF: 0.00 AC: 0 AN: 2110

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.50
DANN	Benign	0.28
PhyloP100		-1.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.23		Position offset: -6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2147363; hg19: chr13-52542796;