rs17139617

Variant names:

• chrX-78019362-C-A
• rs17139617
• NM_000052.7:c.2627-882C>A

Your query was ambiguous. Multiple possible variants found:

• chrX-78019362-C-A
• chrX-78019362-C-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000052.7(ATP7A):​c.2627-882C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 111,365 control chromosomes in the GnomAD database, including 3,058 homozygotes. There are 8,856 hemizygotes in GnomAD. 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 0.27 (3058 hom., 8856 hem., cov: 22)
• Consequence: ATP7A NM_000052.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.267
• Publications: 2 publications found

Genes affected

ATP7A (HGNC:869): (ATPase copper transporting alpha) This gene encodes a transmembrane protein that functions in copper transport across membranes. This protein is localized to the trans Golgi network, where it is predicted to supply copper to copper-dependent enzymes in the secretory pathway. It relocalizes to the plasma membrane under conditions of elevated extracellular copper, and functions in the efflux of copper from cells. Mutations in this gene are associated with Menkes disease, X-linked distal spinal muscular atrophy, and occipital horn syndrome. Alternatively-spliced transcript variants have been observed. [provided by RefSeq, Aug 2013]

PGK1 (HGNC:8896): (phosphoglycerate kinase 1) The protein encoded by this gene is a glycolytic enzyme that catalyzes the conversion of 1,3-diphosphoglycerate to 3-phosphoglycerate. The encoded protein may also act as a cofactor for polymerase alpha. Additionally, this protein is secreted by tumor cells where it participates in angiogenesis by functioning to reduce disulfide bonds in the serine protease, plasmin, which consequently leads to the release of the tumor blood vessel inhibitor angiostatin. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. Deficiency of the enzyme is associated with a wide range of clinical phenotypes hemolytic anemia and neurological impairment. Pseudogenes of this gene have been defined on chromosomes 19, 21 and the X chromosome. [provided by RefSeq, Jan 2014]

PGK1 Gene-Disease associations (from GenCC):

• glycogen storage disease due to phosphoglycerate kinase 1 deficiency

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000052.7. 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
	ATP7A	NM_000052.7	MANE Select	c.2627-882C>A		intron	N/A	NP_000043.4	Q04656-1
	ATP7A	NM_001282224.2		c.2393-882C>A		intron	N/A	NP_001269153.1	Q04656-5
	ATP7A	NR_104109.2		n.285-12038C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP7A	ENST00000341514.11	TSL:1 MANE Select	c.2627-882C>A		intron	N/A	ENSP00000345728.6	Q04656-1
	ATP7A	ENST00000689767.1		c.2720-882C>A		intron	N/A	ENSP00000509406.1	A0A8I5KWA8
	ATP7A	ENST00000343533.10	TSL:5	c.2657-882C>A		intron	N/A	ENSP00000343026.6	A0A8J9FM07

Frequencies

GnomAD3 genomes AF: 0.265 AC: 29551 AN: 111311 Hom.: 3059 Cov.: 22

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.300

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.266 AC: 29570 AN: 111365 Hom.: 3058 Cov.: 22 AF XY: 0.264 AC XY: 8856 AN XY: 33585

African (AFR) AF: 0.376 AC: 11496 AN: 30605

American (AMR) AF: 0.231 AC: 2432 AN: 10525

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 460 AN: 2639

East Asian (EAS) AF: 0.290 AC: 1024 AN: 3525

South Asian (SAS) AF: 0.353 AC: 951 AN: 2691

European-Finnish (FIN) AF: 0.225 AC: 1339 AN: 5950

Middle Eastern (MID) AF: 0.292 AC: 64 AN: 219

European-Non Finnish (NFE) AF: 0.213 AC: 11278 AN: 53019

Other (OTH) AF: 0.252 AC: 383 AN: 1521

Alfa AF: 0.224 Hom.: 3638

Bravo AF: 0.269

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.3
DANN	Benign	0.65
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

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: rs17139617; hg19: chrX-77274859;