20-57560878-C-G

Variant names:

• chr20-57560878-C-G
• rs2071023
• ENST00000851909.1:c.-534C>G

Variant summary

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

The ENST00000851909.1(PCK1):​c.-534C>G variant causes a 5 prime UTR 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 ENST00000851909.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0870
• Publications: 12 publications found

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 Gene-Disease associations (from GenCC):

• phosphoenolpyruvate carboxykinase deficiency, cytosolic

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• phosphoenolpyruvate carboxykinase deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000851909.1. 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
	PCK1	NM_002591.4	MANE Select	c.-366C>G		upstream_gene	N/A	NP_002582.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCK1	ENST00000851909.1		c.-534C>G		5_prime_UTR	Exon 1 of 9	ENSP00000521968.1
	PCK1	ENST00000319441.6	TSL:1 MANE Select	c.-366C>G		upstream_gene	N/A	ENSP00000319814.4	P35558-1
	PCK1	ENST00000467047.1	TSL:1	n.-202C>G		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61618 AN: 151930 Hom.: 12911 Cov.: 32

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.: 32 AF XY: 0.403 AC XY: 29969 AN XY: 74318

African (AFR) AF: 0.310 AC: 12877 AN: 41482

American (AMR) AF: 0.376 AC: 5741 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 1540 AN: 3470

East Asian (EAS) AF: 0.372 AC: 1917 AN: 5158

South Asian (SAS) AF: 0.428 AC: 2067 AN: 4826

European-Finnish (FIN) AF: 0.458 AC: 4832 AN: 10558

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.457 AC: 31068 AN: 67958

Other (OTH) AF: 0.429 AC: 906 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	2.1
DANN	Benign	0.54
PhyloP100		-0.087
PromoterAI		-0.00030	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2071023; hg19: chr20-56135934;