rs717689

Variant names:

• chrX-78124438-C-T
• rs717689
• NM_000291.4:c.937-436C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000291.4(PGK1):​c.937-436C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0953 in 110,429 control chromosomes in the GnomAD database, including 480 homozygotes. There are 3,021 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.095 (480 hom., 3021 hem., cov: 22)
• Consequence: PGK1 NM_000291.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0210
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGK1	NM_000291.4	c.937-436C>T		intron_variant	Intron 8 of 10	ENST00000373316.5	NP_000282.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGK1	ENST00000373316.5	c.937-436C>T		intron_variant	Intron 8 of 10	1	NM_000291.4	ENSP00000362413.4
PGK1	ENST00000644362.1	c.853-436C>T		intron_variant	Intron 8 of 10			ENSP00000496140.1

Frequencies

GnomAD3 genomes AF: 0.0953 AC: 10521 AN: 110378 Hom.: 478 Cov.: 22

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0867

Gnomad ASJ AF: 0.0772

Gnomad EAS AF: 0.0814

Gnomad SAS AF: 0.0892

Gnomad FIN AF: 0.0787

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.0614

Gnomad OTH AF: 0.0903

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

GnomAD4 genome AF: 0.0953 AC: 10528 AN: 110429 Hom.: 480 Cov.: 22 AF XY: 0.0924 AC XY: 3021 AN XY: 32693

African (AFR) AF: 0.167 AC: 5040 AN: 30257

American (AMR) AF: 0.0866 AC: 897 AN: 10359

Ashkenazi Jewish (ASJ) AF: 0.0772 AC: 203 AN: 2629

East Asian (EAS) AF: 0.0814 AC: 285 AN: 3502

South Asian (SAS) AF: 0.0895 AC: 233 AN: 2602

European-Finnish (FIN) AF: 0.0787 AC: 458 AN: 5823

Middle Eastern (MID) AF: 0.120 AC: 26 AN: 217

European-Non Finnish (NFE) AF: 0.0614 AC: 3245 AN: 52867

Other (OTH) AF: 0.0885 AC: 132 AN: 1492

Alfa AF: 0.0734 Hom.: 5486

Bravo AF: 0.101

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.38
PhyloP100		0.021
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: rs717689; hg19: chrX-77379935;