rs879255499

Variant names:

• chr13-52011761-GCGGTCTCGGCCACCT-G
• rs879255499
• NM_001406512.1:c.-174_-160delAGGTGGCCGAGACCG

Variant summary

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

The NM_001406512.1(ATP7B):​c.-174_-160delAGGTGGCCGAGACCG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: not found (cov: 34)
• Consequence: ATP7B NM_001406512.1 5_prime_UTR
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 1.33
• Publications: 1 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 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP7B	NM_001406512.1	c.-174_-160delAGGTGGCCGAGACCG		5_prime_UTR_variant	Exon 1 of 22		NP_001393441.1
ATP7B	NM_001406516.1	c.-174_-160delAGGTGGCCGAGACCG		5_prime_UTR_variant	Exon 1 of 22		NP_001393445.1
ATP7B	NM_001406522.1	c.-174_-160delAGGTGGCCGAGACCG		5_prime_UTR_variant	Exon 1 of 22		NP_001393451.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP7B	ENST00000713659.1	c.-439_-425delAGGTGGCCGAGACCG		5_prime_UTR_variant	Exon 1 of 17			ENSP00000518961.1
ATP7B	ENST00000635406.1	n.106+244_106+258delAGGTGGCCGAGACCG		intron_variant	Intron 1 of 3	4
ATP7B	ENST00000448424.7	c.-439_-425delAGGTGGCCGAGACCG		upstream_gene_variant		1		ENSP00000416738.3
ATP7B	ENST00000673864.2	n.-439_-425delAGGTGGCCGAGACCG		upstream_gene_variant				ENSP00000501045.2

Frequencies

GnomAD3 genomes Cov.: 34

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 34

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

Wilson disease Other:1

-

GeneReviews

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3

Splicing

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

Other links and lift over

dbSNP: rs879255499; hg19: chr13-52585897;