rs1042531

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000467047.1(PCK1):n.4631T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 688,420 control chromosomes in the GnomAD database, including 53,196 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 0.44 ( 16795 hom., cov: 31)

Exomes 𝑓: 0.36 ( 36401 hom. )

Consequence

PCK1
ENST00000467047.1 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.03

Publications

17 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCK1	NM_002591.4 link	c.*120T>G		3_prime_UTR_variant	Exon 10 of 10	ENST00000319441.6	NP_002582.3	P35558-1
PCK1	XM_024451888.2 link	c.*120T>G		3_prime_UTR_variant	Exon 9 of 9		XP_024307656.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCK1	ENST00000467047.1 link	n.4631T>G		non_coding_transcript_exon_variant	Exon 2 of 2	1
PCK1	ENST00000319441.6 link	c.*120T>G		3_prime_UTR_variant	Exon 10 of 10	1	NM_002591.4	ENSP00000319814.4		P35558-1

Frequencies

GnomAD3 genomes

AF:

0.443

AC:

67269

AN:

151852

Hom.:

16777

Cov.:

show subpopulations

Gnomad AFR

AF:

0.684

Gnomad AMI

AF:

0.505

Gnomad AMR

AF:

0.322

Gnomad ASJ

AF:

0.293

Gnomad EAS

AF:

0.257

Gnomad SAS

AF:

0.300

Gnomad FIN

AF:

0.358

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.368

Gnomad OTH

AF:

0.435

GnomAD4 exome

AF:

0.359

AC:

192682

AN:

536450

Hom.:

36401

Cov.:

AF XY:

0.356

AC XY:

98722

AN XY:

277536

show subpopulations

African (AFR)

AF:

0.688

AC:

9692

AN:

14096

American (AMR)

AF:

0.273

AC:

4986

AN:

18262

Ashkenazi Jewish (ASJ)

AF:

0.315

AC:

4488

AN:

14268

East Asian (EAS)

AF:

0.195

AC:

6128

AN:

31432

South Asian (SAS)

AF:

0.310

AC:

13741

AN:

44292

European-Finnish (FIN)

AF:

0.369

AC:

11576

AN:

31390

Middle Eastern (MID)

AF:

0.415

AC:

1405

AN:

3386

European-Non Finnish (NFE)

AF:

0.370

AC:

129574

AN:

350158

Other (OTH)

AF:

0.380

AC:

11092

AN:

29166

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

5989

11978

17967

23956

29945

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.443

AC:

67327

AN:

151970

Hom.:

16795

Cov.:

AF XY:

0.436

AC XY:

32356

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.684

AC:

28332

AN:

41418

American (AMR)

AF:

0.322

AC:

4914

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.293

AC:

1016

AN:

3468

East Asian (EAS)

AF:

0.257

AC:

1326

AN:

5168

South Asian (SAS)

AF:

0.299

AC:

1440

AN:

4820

European-Finnish (FIN)

AF:

0.358

AC:

3776

AN:

10558

Middle Eastern (MID)

AF:

0.412

AC:

121

AN:

294

European-Non Finnish (NFE)

AF:

0.368

AC:

25027

AN:

67950

Other (OTH)

AF:

0.433

AC:

914

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1731

3461

5192

6922

8653

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.397

Hom.:

16238

Bravo

AF:

0.452

Asia WGS

AF:

0.289

AC:

1004

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 13, 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

-0.83

CADD

Benign

0.095

(source)

DANN

Benign

0.55

PhyloP100

-1.0

Mutation Taster

=100/0

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.

rs1042531

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