rs1143692

chr2-46151070-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005400.3(PRKCE):c.1761C>T(p.Ser587=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0512 in 1,599,166 control chromosomes in the GnomAD database, including 2,414 homozygotes. 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: 𝑓 0.041 (156 hom., cov: 31)
  • Exomes 𝑓: 0.052 (2258 hom.)
• Consequence: PRKCE NM_005400.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.43

Genes affected

PRKCE (HGNC:9401): (protein kinase C epsilon) Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and the second messenger diacylglycerol. PKC family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. PKC family members also serve as major receptors for phorbol esters, a class of tumor promoters. Each member of the PKC family has a specific expression profile and is believed to play a distinct role in cells. The protein encoded by this gene is one of the PKC family members. This kinase has been shown to be involved in many different cellular functions, such as neuron channel activation, apoptosis, cardioprotection from ischemia, heat shock response, as well as insulin exocytosis. Knockout studies in mice suggest that this kinase is important for lipopolysaccharide (LPS)-mediated signaling in activated macrophages and may also play a role in controlling anxiety-like behavior. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=-3.43 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKCE	NM_005400.3	c.1761C>T	p.Ser587=	synonymous_variant	13/15	ENST00000306156.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCE	ENST00000306156.8	c.1761C>T	p.Ser587=	synonymous_variant	13/15	1	NM_005400.3	P1

Frequencies

GnomAD3 genomes AF: 0.0408 AC: 6202 AN: 151982 Hom.: 156 Cov.: 31

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0565

Gnomad ASJ AF: 0.0715

Gnomad EAS AF: 0.00771

Gnomad SAS AF: 0.0696

Gnomad FIN AF: 0.0373

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0548

Gnomad OTH AF: 0.0550

GnomAD3 exomes AF: 0.0516 AC: 12184 AN: 236242 Hom.: 427 AF XY: 0.0549 AC XY: 7083 AN XY: 129108

Gnomad AFR exome AF: 0.00915

Gnomad AMR exome AF: 0.0576

Gnomad ASJ exome AF: 0.0731

Gnomad EAS exome AF: 0.00576

Gnomad SAS exome AF: 0.0717

Gnomad FIN exome AF: 0.0398

Gnomad NFE exome AF: 0.0560

Gnomad OTH exome AF: 0.0619

GnomAD4 exome AF: 0.0523 AC: 75678 AN: 1447066 Hom.: 2258 Cov.: 32 AF XY: 0.0532 AC XY: 38302 AN XY: 720234

Gnomad4 AFR exome AF: 0.00863

Gnomad4 AMR exome AF: 0.0588

Gnomad4 ASJ exome AF: 0.0713

Gnomad4 EAS exome AF: 0.00584

Gnomad4 SAS exome AF: 0.0724

Gnomad4 FIN exome AF: 0.0434

Gnomad4 NFE exome AF: 0.0530

Gnomad4 OTH exome AF: 0.0543

GnomAD4 genome AF: 0.0408 AC: 6209 AN: 152100 Hom.: 156 Cov.: 31 AF XY: 0.0405 AC XY: 3014 AN XY: 74350

Gnomad4 AFR AF: 0.0104

Gnomad4 AMR AF: 0.0566

Gnomad4 ASJ AF: 0.0715

Gnomad4 EAS AF: 0.00773

Gnomad4 SAS AF: 0.0703

Gnomad4 FIN AF: 0.0373

Gnomad4 NFE AF: 0.0548

Gnomad4 OTH AF: 0.0553

Alfa AF: 0.0529 Hom.: 52

Bravo AF: 0.0393

Asia WGS AF: 0.0430 AC: 151 AN: 3478

EpiCase AF: 0.0599

EpiControl AF: 0.0590

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
Cadd	Benign	0.53
Dann	Benign	0.83

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: rs1143692; hg19: chr2-46378209; COSMIC: COSV60332867; COSMIC: COSV60332867;