Genetic Variant PCK1:c.-366C>G (chr20-57560878-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002591.4(PCK1):c.-366C>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 152,048 control chromosomes in the GnomAD database, including 12,904 homozygotes. 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 0.41 ( 12904 hom., cov: 32)

Consequence

PCK1
NM_002591.4 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0870

Variant links:

Genes affected

PCK1 (HGNC:8724): (phosphoenolpyruvate carboxykinase 1) This gene is a main control point for the regulation of gluconeogenesis. The cytosolic enzyme encoded by this gene, along with GTP, catalyzes the formation of phosphoenolpyruvate from oxaloacetate, with the release of carbon dioxide and GDP. The expression of this gene can be regulated by insulin, glucocorticoids, glucagon, cAMP, and diet. Defects in this gene are a cause of cytosolic phosphoenolpyruvate carboxykinase deficiency. A mitochondrial isozyme of the encoded protein also has been characterized. [provided by RefSeq, Jul 2008]

PCK1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCK1	NM_002591.4 link	c.-366C>G		upstream_gene_variant		ENST00000319441.6	NP_002582.3	P35558-1
PCK1	XM_024451888.2 link	c.-580C>G		upstream_gene_variant			XP_024307656.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
PCK1	ENST00000319441.6 link	c.-366C>G	upstream_gene_variant	1	NM_002591.4	ENSP00000319814.4	P35558-1
PCK1	ENST00000467047.1 link	n.-202C>G	upstream_gene_variant	1
PCK1	ENST00000475833.1 link	n.-225C>G	upstream_gene_variant	2

Frequencies

GnomAD3 genomes

AF:

0.406

AC:

61618

AN:

151930

Hom.:

12911

Cov.:

show subpopulations

Gnomad AFR

AF:

0.311

Gnomad AMI

AF:

0.546

Gnomad AMR

AF:

0.376

Gnomad ASJ

AF:

0.444

Gnomad EAS

AF:

0.372

Gnomad SAS

AF:

0.430

Gnomad FIN

AF:

0.458

Gnomad MID

AF:

0.554

Gnomad NFE

AF:

0.457

Gnomad OTH

AF:

0.433

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

GnomAD4 genome

AF:

0.405

AC:

61607

AN:

152048

Hom.:

12904

Cov.:

AF XY:

0.403

AC XY:

29969

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.310

Gnomad4 AMR

AF:

0.376

Gnomad4 ASJ

AF:

0.444

Gnomad4 EAS

AF:

0.372

Gnomad4 SAS

AF:

0.428

Gnomad4 FIN

AF:

0.458

Gnomad4 NFE

AF:

0.457

Gnomad4 OTH

AF:

0.429

Alfa

AF:

0.302

Hom.:

822

Bravo

AF:

0.396

Asia WGS

AF:

0.380

AC:

1322

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

2.1

DANN

Benign

0.54

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over