rs717689

Positions:

• chrX-78124438-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
PGK1	NM_000291.4	c.937-436C>T		intron_variant		ENST00000373316.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGK1	ENST00000373316.5	c.937-436C>T		intron_variant		1	NM_000291.4	P1
PGK1	ENST00000644362.1	c.853-436C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0953 AC: 10521 AN: 110378 Hom.: 478 Cov.: 22 AF XY: 0.0926 AC XY: 3021 AN XY: 32632

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

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.0866

Gnomad4 ASJ AF: 0.0772

Gnomad4 EAS AF: 0.0814

Gnomad4 SAS AF: 0.0895

Gnomad4 FIN AF: 0.0787

Gnomad4 NFE AF: 0.0614

Gnomad4 OTH AF: 0.0885

Alfa AF: 0.0667 Hom.: 3836

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs717689; hg19: chrX-77379935;