rs1023049

Positions:

• chr20-57564911-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000319441.6(PCK1):​c.1319-129C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 755,900 control chromosomes in the GnomAD database, including 73,477 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (13729 hom., cov: 33)
  • Exomes 𝑓: 0.44 (59748 hom.)
• Consequence: PCK1 ENST00000319441.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.04

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 20-57564911-C-T is Benign according to our data. Variant chr20-57564911-C-T is described in ClinVar as [Benign]. Clinvar id is 1181378.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCK1	NM_002591.4	c.1319-129C>T		intron_variant		ENST00000319441.6	NP_002582.3
PCK1	XM_024451888.2	c.923-129C>T		intron_variant			XP_024307656.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCK1	ENST00000319441.6	c.1319-129C>T		intron_variant		1	NM_002591.4	ENSP00000319814	P1
PCK1	ENST00000467047.1	n.3832C>T		non_coding_transcript_exon_variant	1/2	1
PCK1	ENST00000485958.1	n.443-129C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63793 AN: 151968 Hom.: 13718 Cov.: 33

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.404

GnomAD4 exome AF: 0.441 AC: 266387 AN: 603814 Hom.: 59748 Cov.: 8 AF XY: 0.439 AC XY: 138643 AN XY: 315982

Gnomad4 AFR exome AF: 0.355

Gnomad4 AMR exome AF: 0.506

Gnomad4 ASJ exome AF: 0.417

Gnomad4 EAS exome AF: 0.651

Gnomad4 SAS exome AF: 0.405

Gnomad4 FIN exome AF: 0.451

Gnomad4 NFE exome AF: 0.428

Gnomad4 OTH exome AF: 0.432

GnomAD4 genome AF: 0.420 AC: 63851 AN: 152086 Hom.: 13729 Cov.: 33 AF XY: 0.424 AC XY: 31512 AN XY: 74348

Gnomad4 AFR AF: 0.359

Gnomad4 AMR AF: 0.470

Gnomad4 ASJ AF: 0.425

Gnomad4 EAS AF: 0.650

Gnomad4 SAS AF: 0.416

Gnomad4 FIN AF: 0.440

Gnomad4 NFE AF: 0.427

Gnomad4 OTH AF: 0.407

Alfa AF: 0.419 Hom.: 13992

Bravo AF: 0.420

Asia WGS AF: 0.530 AC: 1846 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 13, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.62

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: rs1023049; hg19: chr20-56139967; COSMIC: COSV60131728; COSMIC: COSV60131728;