rs371747549

Variant names:

• chrX-78023474-AT-A
• rs371747549
• NM_000052.7:c.2916+2402delT

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 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: Labcorp Genetics (formerly Invitae), Orphanet, G2P, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
ATP7A	NM_000052.7	c.2916+2402delT		intron_variant	Intron 14 of 22	ENST00000341514.11	NP_000043.4
ATP7A	NM_001282224.2	c.2682+2402delT		intron_variant	Intron 13 of 21		NP_001269153.1
ATP7A	NR_104109.2	n.285-7919delT		intron_variant	Intron 2 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP7A	ENST00000341514.11	c.2916+2396delT		intron_variant	Intron 14 of 22	1	NM_000052.7	ENSP00000345728.6

Frequencies

GnomAD3 genomes AF: 0.254 AC: 27925 AN: 109805 Hom.: 2746 Cov.: 15

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

African (AFR) AF: 0.339 AC: 10231 AN: 30157

American (AMR) AF: 0.225 AC: 2330 AN: 10338

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 461 AN: 2620

East Asian (EAS) AF: 0.297 AC: 1029 AN: 3470

South Asian (SAS) AF: 0.344 AC: 908 AN: 2637

European-Finnish (FIN) AF: 0.217 AC: 1227 AN: 5659

Middle Eastern (MID) AF: 0.290 AC: 62 AN: 214

European-Non Finnish (NFE) AF: 0.213 AC: 11181 AN: 52588

Other (OTH) AF: 0.244 AC: 365 AN: 1495

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

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.65
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: rs371747549; hg19: chrX-77278971;