rs1040566

chr20-57562631-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002591.4(PCK1):c.407-65A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,401,362 control chromosomes in the GnomAD database, including 9,549 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (2404 hom., cov: 33)
  • Exomes 𝑓: 0.097 (7145 hom.)
• Consequence: PCK1 NM_002591.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.25

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 20-57562631-A-C is Benign according to our data. Variant chr20-57562631-A-C is described in ClinVar as [Benign]. Clinvar id is 1224911.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCK1	NM_002591.4	c.407-65A>C		intron_variant		ENST00000319441.6
PCK1	XM_024451888.2	c.11-65A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCK1	ENST00000319441.6	c.407-65A>C		intron_variant		1	NM_002591.4	P1
PCK1	ENST00000467047.1	n.1552A>C		non_coding_transcript_exon_variant	1/2	1
PCK1	ENST00000498194.1	n.284A>C		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23035 AN: 151988 Hom.: 2398 Cov.: 33

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.0868

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.0330

Gnomad FIN AF: 0.0923

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0979

Gnomad OTH AF: 0.144

GnomAD4 exome AF: 0.0974 AC: 121662 AN: 1249256 Hom.: 7145 Cov.: 17 AF XY: 0.0949 AC XY: 59096 AN XY: 623040

Gnomad4 AFR exome AF: 0.303

Gnomad4 AMR exome AF: 0.0656

Gnomad4 ASJ exome AF: 0.115

Gnomad4 EAS exome AF: 0.0759

Gnomad4 SAS exome AF: 0.0333

Gnomad4 FIN exome AF: 0.0998

Gnomad4 NFE exome AF: 0.0973

Gnomad4 OTH exome AF: 0.109

GnomAD4 genome AF: 0.152 AC: 23061 AN: 152106 Hom.: 2404 Cov.: 33 AF XY: 0.148 AC XY: 11016 AN XY: 74356

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.0864

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.0328

Gnomad4 FIN AF: 0.0923

Gnomad4 NFE AF: 0.0979

Gnomad4 OTH AF: 0.147

Alfa AF: 0.106 Hom.: 1364

Bravo AF: 0.162

Asia WGS AF: 0.0780 AC: 270 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.013
Dann	Benign	0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs1040566; hg19: chr20-56137687;