rs1042531

Variant names:

• chr20-57565924-T-G
• rs1042531
• ENST00000467047.1:n.4631T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (16795 hom., cov: 31)
  • Exomes 𝑓: 0.36 (36401 hom.)
• Consequence: PCK1 ENST00000467047.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.03
• Publications: 17 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 20-57565924-T-G is Benign according to our data. Variant chr20-57565924-T-G is described in ClinVar as Benign. ClinVar VariationId is 338898.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000467047.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCK1	NM_002591.4	MANE Select	c.*120T>G		3_prime_UTR	Exon 10 of 10	NP_002582.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCK1	ENST00000467047.1	TSL:1	n.4631T>G		non_coding_transcript_exon	Exon 2 of 2
	PCK1	ENST00000319441.6	TSL:1 MANE Select	c.*120T>G		3_prime_UTR	Exon 10 of 10	ENSP00000319814.4

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67269 AN: 151852 Hom.: 16777 Cov.: 31

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.: 7 AF XY: 0.356 AC XY: 98722 AN XY: 277536

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

GnomAD4 genome AF: 0.443 AC: 67327 AN: 151970 Hom.: 16795 Cov.: 31 AF XY: 0.436 AC XY: 32356 AN XY: 74280

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

Alfa AF: 0.397 Hom.: 16238

Bravo AF: 0.452

Asia WGS AF: 0.289 AC: 1004 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Phosphoenolpyruvate carboxykinase deficiency, cytosolic (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.095
DANN	Benign	0.55
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1042531; hg19: chr20-56140980; COSMIC: COSV60127701; COSMIC: COSV60127701;