Variant rs2076628 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.639

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	Protein	UniProt
PGK1	ENST00000644362.1 link	c.-19-6042G>A	intron_variant		ENSP00000496140.1	P00558-2
PGK1	ENST00000477335.5 link	n.202-6042G>A	intron_variant	3
PGK1	ENST00000491291.1 link	n.58-6042G>A	intron_variant	5

Frequencies

GnomAD3 genomes

AF:

0.270

AC:

30127

AN:

111418

Hom.:

3135

Cov.:

AF XY:

0.266

AC XY:

8962

AN XY:

33634

show subpopulations

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.:

AF XY:

0.267

AC XY:

8990

AN XY:

33695

show subpopulations

Gnomad4 AFR

AF:

0.360

Gnomad4 AMR

AF:

0.334

Gnomad4 ASJ

AF:

0.174

Gnomad4 EAS

AF:

0.301

Gnomad4 SAS

AF:

0.307

Gnomad4 FIN

AF:

0.221

Gnomad4 NFE

AF:

0.212

Gnomad4 OTH

AF:

0.267

Alfa

AF:

0.0784

Hom.:

336

Bravo

AF:

0.285

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

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

-0.77

CADD

Benign

5.6

DANN

Benign

0.87

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over