chr20-57562128-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

26 publications found

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 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

PCK1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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

GnomAD2 exomes

AF:

0.172

AC:

43260

AN:

251326

AF XY:

0.176

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 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

African (AFR)

AF:

0.126

AC:

4221

AN:

33478

American (AMR)

AF:

0.129

AC:

5775

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.173

AC:

4531

AN:

26136

East Asian (EAS)

AF:

0.00509

AC:

202

AN:

39700

South Asian (SAS)

AF:

0.171

AC:

14770

AN:

86250

European-Finnish (FIN)

AF:

0.223

AC:

11936

AN:

53414

Middle Eastern (MID)

AF:

0.153

AC:

884

AN:

5768

European-Non Finnish (NFE)

AF:

0.204

AC:

226495

AN:

1111656

Other (OTH)

AF:

0.173

AC:

10471

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

11611

23222

34834

46445

58056

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7652

15304

22956

30608

38260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.172

AC:

26099

AN:

152156

Hom.:

2424

Cov.:

AF XY:

0.170

AC XY:

12649

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.130

AC:

5388

AN:

41498

American (AMR)

AF:

0.144

AC:

2195

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.170

AC:

591

AN:

3468

East Asian (EAS)

AF:

0.0112

AC:

AN:

5186

South Asian (SAS)

AF:

0.154

AC:

746

AN:

4830

European-Finnish (FIN)

AF:

0.219

AC:

2317

AN:

10580

Middle Eastern (MID)

AF:

0.150

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.209

AC:

14213

AN:

67986

Other (OTH)

AF:

0.156

AC:

330

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1112

2225

3337

4450

5562

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

292

584

876

1168

1460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.191

Hom.:

9502

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

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

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

(source)

DANN

Benign

0.76

PhyloP100

0.47

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over