chr2-46151070-C-T

Variant names:

• chr2-46151070-C-T
• rs1143692
• NM_005400.3:c.1761C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005400.3(PRKCE):​c.1761C>T​(p.Ser587Ser) 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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PRKCE	NM_005400.3	c.1761C>T	p.Ser587Ser	synonymous_variant	Exon 13 of 15	ENST00000306156.8	NP_005391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCE	ENST00000306156.8	c.1761C>T	p.Ser587Ser	synonymous_variant	Exon 13 of 15	1	NM_005400.3	ENSP00000306124.3

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

GnomAD2 exomes AF: 0.0516 AC: 12184 AN: 236242 AF XY: 0.0549

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 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

African (AFR) AF: 0.00863 AC: 289 AN: 33476

American (AMR) AF: 0.0588 AC: 2628 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.0713 AC: 1861 AN: 26118

East Asian (EAS) AF: 0.00584 AC: 232 AN: 39694

South Asian (SAS) AF: 0.0724 AC: 6241 AN: 86200

European-Finnish (FIN) AF: 0.0434 AC: 1699 AN: 39132

Middle Eastern (MID) AF: 0.0842 AC: 485 AN: 5762

European-Non Finnish (NFE) AF: 0.0530 AC: 58971 AN: 1111700

Other (OTH) AF: 0.0543 AC: 3272 AN: 60298

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

African (AFR) AF: 0.0104 AC: 431 AN: 41504

American (AMR) AF: 0.0566 AC: 864 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0715 AC: 248 AN: 3470

East Asian (EAS) AF: 0.00773 AC: 40 AN: 5174

South Asian (SAS) AF: 0.0703 AC: 338 AN: 4806

European-Finnish (FIN) AF: 0.0373 AC: 394 AN: 10574

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0548 AC: 3726 AN: 67984

Other (OTH) AF: 0.0553 AC: 117 AN: 2114

Alfa AF: 0.0432 Hom.: 111

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
PhyloP100		-3.4
Mutation Taster		=99/1	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: rs1143692; hg19: chr2-46378209; COSMIC: COSV60332867; COSMIC: COSV60332867;