rs2179706

Variant names:

• chr20-57564815-C-T
• rs2179706
• NM_002591.4:c.1318+202C>T

Variant summary

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

The NM_002591.4(PCK1):​c.1318+202C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 619,532 control chromosomes in the GnomAD database, including 68,335 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.45 (15388 hom., cov: 33)
  • Exomes 𝑓: 0.47 (52947 hom.)
• Consequence: PCK1 NM_002591.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.635
• Publications: 16 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=-0.9).
• BP6: Variant 20-57564815-C-T is Benign according to our data. Variant chr20-57564815-C-T is described in ClinVar as Benign. ClinVar VariationId is 1269048.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.635 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.1318+202C>T		intron	N/A	NP_002582.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCK1	ENST00000319441.6	TSL:1 MANE Select	c.1318+202C>T		intron	N/A	ENSP00000319814.4	P35558-1
	PCK1	ENST00000467047.1	TSL:1	n.3736C>T		non_coding_transcript_exon	Exon 1 of 2
	PCK1	ENST00000851909.1		c.1318+202C>T		intron	N/A	ENSP00000521968.1

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67670 AN: 151984 Hom.: 15377 Cov.: 33

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.653

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.430

GnomAD4 exome AF: 0.471 AC: 220116 AN: 467430 Hom.: 52947 Cov.: 5 AF XY: 0.467 AC XY: 114521 AN XY: 245124

African (AFR) AF: 0.365 AC: 4675 AN: 12808

American (AMR) AF: 0.503 AC: 8687 AN: 17258

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 6116 AN: 13792

East Asian (EAS) AF: 0.651 AC: 20280 AN: 31162

South Asian (SAS) AF: 0.411 AC: 18078 AN: 44008

European-Finnish (FIN) AF: 0.476 AC: 15033 AN: 31576

Middle Eastern (MID) AF: 0.362 AC: 723 AN: 1998

European-Non Finnish (NFE) AF: 0.466 AC: 134325 AN: 288262

Other (OTH) AF: 0.459 AC: 12199 AN: 26566

GnomAD4 genome AF: 0.445 AC: 67730 AN: 152102 Hom.: 15388 Cov.: 33 AF XY: 0.448 AC XY: 33291 AN XY: 74344

African (AFR) AF: 0.371 AC: 15409 AN: 41494

American (AMR) AF: 0.490 AC: 7493 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1580 AN: 3470

East Asian (EAS) AF: 0.653 AC: 3378 AN: 5172

South Asian (SAS) AF: 0.426 AC: 2057 AN: 4824

European-Finnish (FIN) AF: 0.460 AC: 4868 AN: 10574

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.465 AC: 31600 AN: 67968

Other (OTH) AF: 0.431 AC: 911 AN: 2112

Alfa AF: 0.455 Hom.: 27447

Bravo AF: 0.445

Asia WGS AF: 0.537 AC: 1870 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.41
DANN	Benign	0.23
PhyloP100		-0.64
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2179706;

hg19: chr20-56139871;