rs371747549

Positions:

• chrX-78023474-AT-A
• chrX-78023474-AT-ATT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000052.7(ATP7A):​c.2916+2402delT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.25 (2744 hom., 8119 hem., cov: 15)
• Consequence: ATP7A NM_000052.7 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.647

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]

ATP7A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant X-78023474-AT-A is Benign according to our data. Variant chrX-78023474-AT-A is described in ClinVar as [Likely_benign]. Clinvar id is 254758.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP7A	NM_000052.7	c.2916+2402delT		intron_variant		ENST00000341514.11	NP_000043.4
ATP7A	NM_001282224.2	c.2682+2402delT		intron_variant			NP_001269153.1
ATP7A	NR_104109.2	n.285-7919delT		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP7A	ENST00000341514.11	c.2916+2402delT		intron_variant		1	NM_000052.7	ENSP00000345728.6

Frequencies

GnomAD3 genomes AF: 0.254 AC: 27925 AN: 109805 Hom.: 2746 Cov.: 15 AF XY: 0.252 AC XY: 8106 AN XY: 32207

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.298

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.241

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

GnomAD4 genome AF: 0.254 AC: 27940 AN: 109854 Hom.: 2744 Cov.: 15 AF XY: 0.252 AC XY: 8119 AN XY: 32266

Gnomad4 AFR AF: 0.339

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.297

Gnomad4 SAS AF: 0.344

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.244

Alfa AF: 0.0758 Hom.: 329

Bravo AF: 0.257

Asia WGS AF: 0.290 AC: 732 AN: 2520

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

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: rs371747549; hg19: chrX-77278971;