Variant chr20-57566235-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002591.4(PCK1):c.*431T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0862 in 159,590 control chromosomes in the GnomAD database, including 973 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.088 ( 945 hom., cov: 32)

Exomes 𝑓: 0.047 ( 28 hom. )

Consequence

PCK1
NM_002591.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.439

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 20-57566235-T-C is Benign according to our data. Variant chr20-57566235-T-C is described in ClinVar as [Benign]. Clinvar id is 338916.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCK1	NM_002591.4 linkuse as main transcript	c.*431T>C		3_prime_UTR_variant	10/10	ENST00000319441.6	NP_002582.3
PCK1	XM_024451888.2 linkuse as main transcript	c.*431T>C		3_prime_UTR_variant	9/9		XP_024307656.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCK1	ENST00000319441.6 linkuse as main transcript	c.*431T>C		3_prime_UTR_variant	10/10	1	NM_002591.4	ENSP00000319814	P1	P35558-1
PCK1	ENST00000467047.1 linkuse as main transcript	n.4942T>C		non_coding_transcript_exon_variant	2/2	1

Frequencies

GnomAD3 genomes

AF:

0.0881

AC:

13371

AN:

151768

Hom.:

941

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0198

Gnomad AMI

AF:

0.0603

Gnomad AMR

AF:

0.211

Gnomad ASJ

AF:

0.143

Gnomad EAS

AF:

0.263

Gnomad SAS

AF:

0.107

Gnomad FIN

AF:

0.0987

Gnomad MID

AF:

0.179

Gnomad NFE

AF:

0.0826

Gnomad OTH

AF:

0.102

GnomAD4 exome

AF:

0.0472

AC:

364

AN:

7704

Hom.:

Cov.:

AF XY:

0.0481

AC XY:

195

AN XY:

4056

show subpopulations

Gnomad4 AFR exome

AF:

0.00521

Gnomad4 AMR exome

AF:

0.111

Gnomad4 ASJ exome

AF:

0.0588

Gnomad4 EAS exome

AF:

0.0758

Gnomad4 SAS exome

AF:

0.0272

Gnomad4 FIN exome

AF:

0.0589

Gnomad4 NFE exome

AF:

0.0379

Gnomad4 OTH exome

AF:

0.0510

GnomAD4 genome

AF:

0.0882

AC:

13389

AN:

151886

Hom.:

945

Cov.:

AF XY:

0.0936

AC XY:

6945

AN XY:

74226

show subpopulations

Gnomad4 AFR

AF:

0.0197

Gnomad4 AMR

AF:

0.212

Gnomad4 ASJ

AF:

0.143

Gnomad4 EAS

AF:

0.263

Gnomad4 SAS

AF:

0.107

Gnomad4 FIN

AF:

0.0987

Gnomad4 NFE

AF:

0.0826

Gnomad4 OTH

AF:

0.107

Alfa

AF:

0.0913

Hom.:

606

Bravo

AF:

0.0946

Asia WGS

AF:

0.190

AC:

658

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Phosphoenolpyruvate carboxykinase deficiency, cytosolic

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Mar 06, 2018

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.30

DANN

Benign

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

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