chr2-46133768-G-C

Variant names:

• chr2-46133768-G-C
• rs10168349
• NM_005400.3:c.1593-11325G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005400.3(PRKCE):​c.1593-11325G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 152,020 control chromosomes in the GnomAD database, including 10,068 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 0.35 (10068 hom., cov: 32)
• Consequence: PRKCE NM_005400.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127
• Publications: 28 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCE	NM_005400.3	c.1593-11325G>C		intron_variant	Intron 11 of 14	ENST00000306156.8	NP_005391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCE	ENST00000306156.8	c.1593-11325G>C		intron_variant	Intron 11 of 14	1	NM_005400.3	ENSP00000306124.3
PRKCE	ENST00000469753.5	n.680-11325G>C		intron_variant	Intron 2 of 3	3
PRKCE	ENST00000480633.1	n.359-11325G>C		intron_variant	Intron 2 of 3	2

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53707 AN: 151902 Hom.: 10050 Cov.: 32

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.328

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.354 AC: 53767 AN: 152020 Hom.: 10068 Cov.: 32 AF XY: 0.350 AC XY: 25975 AN XY: 74304

African (AFR) AF: 0.461 AC: 19106 AN: 41434

American (AMR) AF: 0.276 AC: 4221 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 1209 AN: 3470

East Asian (EAS) AF: 0.154 AC: 799 AN: 5178

South Asian (SAS) AF: 0.335 AC: 1608 AN: 4800

European-Finnish (FIN) AF: 0.273 AC: 2889 AN: 10578

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22821 AN: 67974

Other (OTH) AF: 0.325 AC: 684 AN: 2106

Alfa AF: 0.337 Hom.: 4857

Bravo AF: 0.355

Asia WGS AF: 0.248 AC: 864 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.9
DANN	Benign	0.25
PhyloP100		-0.13
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

Other links and lift over

dbSNP: rs10168349; hg19: chr2-46360907;