rs797045371

Variant names:

• chrX-78031440-ACGGA-NNNN
• NM_000052.7:c.3152_3156delACGGAinsNNNN

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PVS1

The NM_000052.7(ATP7A):​c.3152_3156delACGGAinsNNNN​(p.His1051fs) variant causes a frameshift, missense change. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. H1051H) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 N/A (N/A hom., N/A hem., cov:)
  • Exomes 𝑓: N/A (N/A hom. N/A hem.)
• Consequence: ATP7A NM_000052.7 frameshift, missense
• Clinical Significance: Not reported in ClinVar
• Conservation: No conservation score assigned
• 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: Likely_pathogenic. The variant received 8 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

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.3152_3156delACGGAinsNNNN	p.His1051fs	frameshift missense	Exon 16 of 23	NP_000043.4
	ATP7A	NM_001282224.2		c.2918_2922delACGGAinsNNNN	p.His973fs	frameshift missense	Exon 15 of 22	NP_001269153.1
	ATP7A	NR_104109.2		n.325_329delACGGAinsNNNN		non_coding_transcript_exon	Exon 3 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP7A	ENST00000341514.11	TSL:1 MANE Select	c.3152_3156delACGGAinsNNNN	p.His1051fs	frameshift missense	Exon 16 of 23	ENSP00000345728.6
	ATP7A	ENST00000689767.1		c.3245_3249delACGGAinsNNNN	p.His1082fs	frameshift missense	Exon 18 of 25	ENSP00000509406.1
	ATP7A	ENST00000343533.10	TSL:5	c.3182_3186delACGGAinsNNNN	p.His1061fs	frameshift missense	Exon 17 of 24	ENSP00000343026.6

Frequencies

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

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Splicing

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

Other links and lift over

hg19: chrX-77286938;