NM_005400.3:c.1593-19066A>G

Variant names:

• chr2-46126027-A-G
• rs10495928
• NM_005400.3:c.1593-19066A>G

Variant summary

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

The NM_005400.3(PRKCE):​c.1593-19066A>G 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 152,168 control chromosomes in the GnomAD database, including 10,049 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 (10049 hom., cov: 33)
• Consequence: PRKCE NM_005400.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.231
• Publications: 33 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=-0.55).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCE	NM_005400.3	c.1593-19066A>G		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.1593-19066A>G		intron_variant	Intron 11 of 14	1	NM_005400.3	ENSP00000306124.3
PRKCE	ENST00000469753.5	n.680-19066A>G		intron_variant	Intron 2 of 3	3
PRKCE	ENST00000480633.1	n.359-19066A>G		intron_variant	Intron 2 of 3	2

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53790 AN: 152050 Hom.: 10030 Cov.: 33

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.334

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

GnomAD4 genome AF: 0.354 AC: 53852 AN: 152168 Hom.: 10049 Cov.: 33 AF XY: 0.350 AC XY: 26030 AN XY: 74402

African (AFR) AF: 0.457 AC: 18983 AN: 41504

American (AMR) AF: 0.278 AC: 4241 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1205 AN: 3470

East Asian (EAS) AF: 0.166 AC: 860 AN: 5176

South Asian (SAS) AF: 0.339 AC: 1637 AN: 4824

European-Finnish (FIN) AF: 0.273 AC: 2893 AN: 10588

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.337 AC: 22904 AN: 68014

Other (OTH) AF: 0.330 AC: 698 AN: 2112

Alfa AF: 0.338 Hom.: 39997

Bravo AF: 0.355

Asia WGS AF: 0.257 AC: 895 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	11
DANN	Benign	0.59
PhyloP100		0.23
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: rs10495928; hg19: chr2-46353166;