NM_002591.4:c.282C>T

Variant names:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_002591.4(PCK1):c.282C>T(p.Ile94Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,613,658 control chromosomes in the GnomAD database, including 30,555 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2424 hom., cov: 33)

Exomes 𝑓: 0.19 ( 28131 hom. )

Consequence

PCK1
NM_002591.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.472

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 20-57562128-C-T is Benign according to our data. Variant chr20-57562128-C-T is described in ClinVar as [Benign]. Clinvar id is 338874.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.472 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCK1	NM_002591.4 link	c.282C>T	p.Ile94Ile	synonymous_variant	Exon 3 of 10	ENST00000319441.6	NP_002582.3	P35558-1
PCK1	XM_024451888.2 link	c.10+493C>T		intron_variant	Intron 2 of 8		XP_024307656.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PCK1	ENST00000319441.6 link	c.282C>T	p.Ile94Ile	synonymous_variant	Exon 3 of 10	1	NM_002591.4	ENSP00000319814.4	P35558-1
PCK1	ENST00000467047.1 link	n.1049C>T		non_coding_transcript_exon_variant	Exon 1 of 2	1
PCK1	ENST00000475833.1 link	n.858C>T		non_coding_transcript_exon_variant	Exon 2 of 2	2
PCK1	ENST00000498194.1 link	n.-220C>T		upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.171

AC:

26059

AN:

152038

Hom.:

2416

Cov.:

show subpopulations

Gnomad AFR

AF:

0.129

Gnomad AMI

AF:

0.238

Gnomad AMR

AF:

0.144

Gnomad ASJ

AF:

0.170

Gnomad EAS

AF:

0.0112

Gnomad SAS

AF:

0.153

Gnomad FIN

AF:

0.219

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.157

GnomAD3 exomes

AF:

0.172

AC:

43260

AN:

251326

Hom.:

4213

AF XY:

0.176

AC XY:

23846

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.125

Gnomad AMR exome

AF:

0.132

Gnomad ASJ exome

AF:

0.170

Gnomad EAS exome

AF:

0.00794

Gnomad SAS exome

AF:

0.170

Gnomad FIN exome

AF:

0.222

Gnomad NFE exome

AF:

0.208

Gnomad OTH exome

AF:

0.185

GnomAD4 exome

AF:

0.191

AC:

279285

AN:

1461502

Hom.:

28131

Cov.:

AF XY:

0.192

AC XY:

139361

AN XY:

727064

show subpopulations

Gnomad4 AFR exome

AF:

0.126

Gnomad4 AMR exome

AF:

0.129

Gnomad4 ASJ exome

AF:

0.173

Gnomad4 EAS exome

AF:

0.00509

Gnomad4 SAS exome

AF:

0.171

Gnomad4 FIN exome

AF:

0.223

Gnomad4 NFE exome

AF:

0.204

Gnomad4 OTH exome

AF:

0.173

GnomAD4 genome

AF:

0.172

AC:

26099

AN:

152156

Hom.:

2424

Cov.:

AF XY:

0.170

AC XY:

12649

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.130

Gnomad4 AMR

AF:

0.144

Gnomad4 ASJ

AF:

0.170

Gnomad4 EAS

AF:

0.0112

Gnomad4 SAS

AF:

0.154

Gnomad4 FIN

AF:

0.219

Gnomad4 NFE

AF:

0.209

Gnomad4 OTH

AF:

0.156

Alfa

AF:

0.195

Hom.:

6685

Bravo

AF:

0.160

Asia WGS

AF:

0.0800

AC:

281

AN:

3478

EpiCase

AF:

0.202

EpiControl

AF:

0.199

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Phosphoenolpyruvate carboxykinase deficiency, cytosolic

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

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