ENST00000644362.1:c.-19-6042G>A

Variant names:

• chrX-78103825-G-A
• rs2076628
• ENST00000644362.1:c.-19-6042G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000644362.1(PGK1):​c.-19-6042G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 111,469 control chromosomes in the GnomAD database, including 3,136 homozygotes. There are 8,990 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.27 (3136 hom., 8990 hem., cov: 24)
• Consequence: PGK1 ENST00000644362.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.639
• Publications: 1 publications found

Genes affected

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant X-78103825-G-A is Benign according to our data. Variant chrX-78103825-G-A is described in ClinVar as Benign. ClinVar VariationId is 683511.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000644362.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGK1	ENST00000644362.1		c.-19-6042G>A		intron	N/A	ENSP00000496140.1
	PGK1	ENST00000477335.5	TSL:3	n.202-6042G>A		intron	N/A
	PGK1	ENST00000491291.1	TSL:5	n.58-6042G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.270 AC: 30127 AN: 111418 Hom.: 3135 Cov.: 24

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.298

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.271 AC: 30160 AN: 111469 Hom.: 3136 Cov.: 24 AF XY: 0.267 AC XY: 8990 AN XY: 33695

African (AFR) AF: 0.360 AC: 11039 AN: 30623

American (AMR) AF: 0.334 AC: 3545 AN: 10612

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 461 AN: 2644

East Asian (EAS) AF: 0.301 AC: 1059 AN: 3520

South Asian (SAS) AF: 0.307 AC: 842 AN: 2740

European-Finnish (FIN) AF: 0.221 AC: 1318 AN: 5952

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

European-Non Finnish (NFE) AF: 0.212 AC: 11244 AN: 52984

Other (OTH) AF: 0.267 AC: 402 AN: 1507

Alfa AF: 0.0784 Hom.: 336

Bravo AF: 0.285

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.6
DANN	Benign	0.87
PhyloP100		0.64
PromoterAI		-0.081	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2076628; hg19: chrX-77359322;