NM_005400.3:c.1144C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005400.3(PRKCE):​c.1144C>T​(p.Pro382Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,447,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P382A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PRKCE
NM_005400.3 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.138
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.032148957).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PRKCENM_005400.3 linkc.1144C>T p.Pro382Ser missense_variant Exon 9 of 15 ENST00000306156.8 NP_005391.1 Q02156L7RTI5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PRKCEENST00000306156.8 linkc.1144C>T p.Pro382Ser missense_variant Exon 9 of 15 1 NM_005400.3 ENSP00000306124.3 Q02156
PRKCEENST00000394874.1 linkc.313C>T p.Pro105Ser missense_variant Exon 4 of 6 3 ENSP00000378341.1 E9PBI2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000422
AC:
1
AN:
236966
Hom.:
0
AF XY:
0.00000772
AC XY:
1
AN XY:
129516
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000896
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.91e-7
AC:
1
AN:
1447434
Hom.:
0
Cov.:
32
AF XY:
0.00000139
AC XY:
1
AN XY:
720436
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000841
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.058
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
0.018
DANN
Benign
0.76
DEOGEN2
Benign
0.19
T;.
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.014
N
LIST_S2
Benign
0.73
T;T
M_CAP
Benign
0.0072
T
MetaRNN
Benign
0.032
T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
-0.34
N;.
PrimateAI
Benign
0.32
T
PROVEAN
Benign
1.1
N;N
REVEL
Benign
0.040
Sift
Benign
0.75
T;T
Sift4G
Benign
0.88
T;T
Polyphen
0.0
B;.
Vest4
0.077
MutPred
0.31
Gain of phosphorylation at P382 (P = 0.0155);.;
MVP
0.28
MPC
0.63
ClinPred
0.028
T
GERP RS
-5.1
Varity_R
0.012
gMVP
0.20

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs763892538; hg19: chr2-46234681; API