20-57562839-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002591.4(PCK1):c.550G>C(p.Val184Leu) variant causes a missense change. The variant allele was found at a frequency of 0.856 in 1,613,292 control chromosomes in the GnomAD database, including 593,332 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.88 ( 59909 hom., cov: 35)

Exomes 𝑓: 0.85 ( 533423 hom. )

Consequence

PCK1
NM_002591.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 4.49

Publications

41 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.0281385E-7).

BP6

Variant 20-57562839-G-C is Benign according to our data. Variant chr20-57562839-G-C is described in ClinVar as Benign. ClinVar VariationId is 338879.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002591.4. 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.550G>C	p.Val184Leu	missense	Exon 4 of 10	NP_002582.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PCK1	ENST00000319441.6	TSL:1 MANE Select	c.550G>C	p.Val184Leu	missense	Exon 4 of 10	ENSP00000319814.4	P35558-1
PCK1	ENST00000467047.1	TSL:1	n.1760G>C		non_coding_transcript_exon	Exon 1 of 2
PCK1	ENST00000851909.1		c.550G>C	p.Val184Leu	missense	Exon 3 of 9	ENSP00000521968.1

Frequencies

GnomAD3 genomes

AF:

0.884

AC:

134596

AN:

152200

Hom.:

59857

Cov.:

show subpopulations

Gnomad AFR

AF:

0.973

Gnomad AMI

AF:

0.928

Gnomad AMR

AF:

0.837

Gnomad ASJ

AF:

0.837

Gnomad EAS

AF:

0.783

Gnomad SAS

AF:

0.742

Gnomad FIN

AF:

0.860

Gnomad MID

AF:

0.918

Gnomad NFE

AF:

0.864

Gnomad OTH

AF:

0.880

GnomAD2 exomes

AF:

0.841

AC:

211380

AN:

251210

AF XY:

0.837

show subpopulations

Gnomad AFR exome

AF:

0.975

Gnomad AMR exome

AF:

0.797

Gnomad ASJ exome

AF:

0.834

Gnomad EAS exome

AF:

0.785

Gnomad FIN exome

AF:

0.867

Gnomad NFE exome

AF:

0.866

Gnomad OTH exome

AF:

0.853

GnomAD4 exome

AF:

0.853

AC:

1246922

AN:

1460974

Hom.:

533423

Cov.:

AF XY:

0.850

AC XY:

618007

AN XY:

726796

show subpopulations

African (AFR)

AF:

0.977

AC:

32721

AN:

33478

American (AMR)

AF:

0.798

AC:

35699

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.837

AC:

21858

AN:

26118

East Asian (EAS)

AF:

0.749

AC:

29751

AN:

39698

South Asian (SAS)

AF:

0.747

AC:

64410

AN:

86210

European-Finnish (FIN)

AF:

0.872

AC:

46556

AN:

53410

Middle Eastern (MID)

AF:

0.883

AC:

5089

AN:

5762

European-Non Finnish (NFE)

AF:

0.863

AC:

959137

AN:

1111218

Other (OTH)

AF:

0.856

AC:

51701

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

9093

18186

27279

36372

45465

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21206

42412

63618

84824

106030

<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:

0.884

AC:

134704

AN:

152318

Hom.:

59909

Cov.:

AF XY:

0.879

AC XY:

65481

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.973

AC:

40488

AN:

41594

American (AMR)

AF:

0.836

AC:

12788

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.837

AC:

2906

AN:

3472

East Asian (EAS)

AF:

0.784

AC:

4057

AN:

5178

South Asian (SAS)

AF:

0.742

AC:

3582

AN:

4826

European-Finnish (FIN)

AF:

0.860

AC:

9125

AN:

10610

Middle Eastern (MID)

AF:

0.918

AC:

270

AN:

294

European-Non Finnish (NFE)

AF:

0.864

AC:

58776

AN:

68016

Other (OTH)

AF:

0.882

AC:

1866

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

805

1611

2416

3222

4027

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

898

1796

2694

3592

4490

<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:

0.859

Hom.:

38121

Bravo

AF:

0.887

TwinsUK

AF:

0.861

AC:

3194

ALSPAC

AF:

0.860

AC:

3314

ESP6500AA

AF:

0.970

AC:

4276

ESP6500EA

AF:

0.866

AC:

7445

ExAC

AF:

0.846

AC:

102732

Asia WGS

AF:

0.774

AC:

2692

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Phosphoenolpyruvate carboxykinase deficiency, cytosolic (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.23

DEOGEN2

Benign

0.057

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.69

MetaRNN

Benign

7.0e-7

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-3.7

PhyloP100

4.5

PrimateAI

Uncertain

0.53

PROVEAN

Benign

1.8

REVEL

Benign

0.16

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.13

MutPred

0.20

Gain of helix (P = 0.132)

MPC

0.092

ClinPred

0.0053

GERP RS

5.1

Varity_R

0.12

gMVP

0.48

Mutation Taster

=81/19

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over