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GeneBe

2-46010445-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_005400.3(PRKCE):c.1365A>G(p.Thr455=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00798 in 1,599,712 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0053 ( 2 hom., cov: 33)
Exomes 𝑓: 0.0083 ( 73 hom. )

Consequence

PRKCE
NM_005400.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.562
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-46010445-A-G is Benign according to our data. Variant chr2-46010445-A-G is described in ClinVar as [Benign]. Clinvar id is 720098.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.562 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 812 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PRKCENM_005400.3 linkuse as main transcriptc.1365A>G p.Thr455= synonymous_variant 10/15 ENST00000306156.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PRKCEENST00000306156.8 linkuse as main transcriptc.1365A>G p.Thr455= synonymous_variant 10/151 NM_005400.3 P1
PRKCEENST00000394874.1 linkuse as main transcriptc.534A>G p.Thr178= synonymous_variant 5/63

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00534
AC:
812
AN:
152190
Hom.:
2
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00186
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00458
Gnomad ASJ
AF:
0.00403
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00122
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00922
Gnomad OTH
AF:
0.00525
GnomAD3 exomes
AF:
0.00508
AC:
1204
AN:
236900
Hom.:
10
AF XY:
0.00500
AC XY:
648
AN XY:
129472
show subpopulations
Gnomad AFR exome
AF:
0.00212
Gnomad AMR exome
AF:
0.00415
Gnomad ASJ exome
AF:
0.00502
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000360
Gnomad FIN exome
AF:
0.00197
Gnomad NFE exome
AF:
0.00821
Gnomad OTH exome
AF:
0.00505
GnomAD4 exome
AF:
0.00826
AC:
11959
AN:
1447404
Hom.:
73
Cov.:
32
AF XY:
0.00799
AC XY:
5754
AN XY:
720416
show subpopulations
Gnomad4 AFR exome
AF:
0.00155
Gnomad4 AMR exome
AF:
0.00458
Gnomad4 ASJ exome
AF:
0.00578
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000209
Gnomad4 FIN exome
AF:
0.00258
Gnomad4 NFE exome
AF:
0.00983
Gnomad4 OTH exome
AF:
0.00821
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00533
AC:
812
AN:
152308
Hom.:
2
Cov.:
33
AF XY:
0.00490
AC XY:
365
AN XY:
74482
show subpopulations
Gnomad4 AFR
AF:
0.00185
Gnomad4 AMR
AF:
0.00458
Gnomad4 ASJ
AF:
0.00403
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00122
Gnomad4 NFE
AF:
0.00922
Gnomad4 OTH
AF:
0.00520
Alfa
AF:
0.00646
Hom.:
0
Bravo
AF:
0.00541
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.00823
EpiControl
AF:
0.00794

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.67
Cadd
Benign
4.6
Dann
Benign
0.64

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs61730655; hg19: chr2-46237584; API