20-57564911-C-A

Variant names:

• chr20-57564911-C-A
• rs1023049
• NM_002591.4:c.1319-129C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002591.4(PCK1):​c.1319-129C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000165 in 604,716 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: PCK1 NM_002591.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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.1319-129C>A		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.1319-129C>A		intron	N/A	ENSP00000319814.4	P35558-1
	PCK1	ENST00000467047.1	TSL:1	n.3832C>A		non_coding_transcript_exon	Exon 1 of 2
	PCK1	ENST00000851909.1		c.1319-129C>A		intron	N/A	ENSP00000521968.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000165 AC: 1 AN: 604716 Hom.: 0 Cov.: 8 AF XY: 0.00000316 AC XY: 1 AN XY: 316440

African (AFR) AF: 0.00 AC: 0 AN: 15812

American (AMR) AF: 0.00 AC: 0 AN: 23904

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15250

East Asian (EAS) AF: 0.00 AC: 0 AN: 34972

South Asian (SAS) AF: 0.00 AC: 0 AN: 52182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46468

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2490

European-Non Finnish (NFE) AF: 0.00000261 AC: 1 AN: 382486

Other (OTH) AF: 0.00 AC: 0 AN: 31152

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.41
DANN	Benign	0.49
PhyloP100		-2.0

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

Other links and lift over

dbSNP: rs1023049; hg19: chr20-56139967;