X-77910952-T-C

Variant names:

• chrX-77910952-T-C
• rs2184780
• NM_000052.7:c.-22+117T>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_000052.7(ATP7A):​c.-22+117T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 1.0 (38824 hom., 32837 hem., cov: 23)
  • Exomes 𝑓: 1.0 (6 hom. 14 hem.)
  • Failed GnomAD Quality Control
• Consequence: ATP7A NM_000052.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.925
• Publications: 1 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

ENSG00000293258 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant X-77910952-T-C is Benign according to our data. Variant chrX-77910952-T-C is described in ClinVar as [Benign]. Clinvar id is 678099.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP7A	NM_000052.7	c.-22+117T>C		intron_variant	Intron 1 of 22	ENST00000341514.11	NP_000043.4
ATP7A	NM_001282224.2	c.-22+117T>C		intron_variant	Intron 1 of 21		NP_001269153.1
ATP7A	NR_104109.2	n.143+117T>C		intron_variant	Intron 1 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP7A	ENST00000341514.11	c.-22+117T>C		intron_variant	Intron 1 of 22	1	NM_000052.7	ENSP00000345728.6

Frequencies

GnomAD3 genomes AF: 0.999 AC: 110529 AN: 110656 Hom.: 38830 Cov.: 23

Gnomad AFR AF: 0.996

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.999

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.999

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 1.00 AC: 26 AN: 26 Hom.: 6 AF XY: 1.00 AC XY: 14 AN XY: 14

African (AFR) AF: 1.00 AC: 1 AN: 1

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 5 AN: 5

Middle Eastern (MID) AF: 1.00 AC: 1 AN: 1

European-Non Finnish (NFE) AF: 1.00 AC: 12 AN: 12

Other (OTH) AF: 1.00 AC: 5 AN: 5

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.999 AC: 110580 AN: 110708 Hom.: 38824 Cov.: 23 AF XY: 0.999 AC XY: 32837 AN XY: 32870

African (AFR) AF: 0.996 AC: 30309 AN: 30424

American (AMR) AF: 0.999 AC: 10417 AN: 10428

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2638 AN: 2638

East Asian (EAS) AF: 1.00 AC: 3490 AN: 3490

South Asian (SAS) AF: 1.00 AC: 2570 AN: 2570

European-Finnish (FIN) AF: 1.00 AC: 5840 AN: 5840

Middle Eastern (MID) AF: 1.00 AC: 217 AN: 217

European-Non Finnish (NFE) AF: 1.00 AC: 52912 AN: 52913

Other (OTH) AF: 0.999 AC: 1509 AN: 1510

Alfa AF: 0.999 Hom.: 9250

Bravo AF: 0.998

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 20, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	12
DANN	Benign	0.48
PhyloP100		0.93
PromoterAI		0.0083	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2184780; hg19: chrX-77166449;