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GeneBe

2-46010391-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_005400.3(PRKCE):c.1311G>A(p.Lys437=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00662 in 1,599,602 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0041 ( 3 hom., cov: 33)
Exomes 𝑓: 0.0069 ( 54 hom. )

Consequence

PRKCE
NM_005400.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.359
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 -9 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=-0.41).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-46010391-G-A is Benign according to our data. Variant chr2-46010391-G-A is described in ClinVar as [Benign]. Clinvar id is 771697.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=0.359 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 630 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PRKCENM_005400.3 linkuse as main transcriptc.1311G>A p.Lys437= synonymous_variant 10/15 ENST00000306156.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PRKCEENST00000306156.8 linkuse as main transcriptc.1311G>A p.Lys437= synonymous_variant 10/151 NM_005400.3 P1
PRKCEENST00000394874.1 linkuse as main transcriptc.480G>A p.Lys160= synonymous_variant 5/63

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00414
AC:
630
AN:
152134
Hom.:
3
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00147
Gnomad AMI
AF:
0.00110
Gnomad AMR
AF:
0.00380
Gnomad ASJ
AF:
0.000577
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000622
Gnomad FIN
AF:
0.00207
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00701
Gnomad OTH
AF:
0.00287
GnomAD3 exomes
AF:
0.00410
AC:
971
AN:
236812
Hom.:
2
AF XY:
0.00406
AC XY:
525
AN XY:
129424
show subpopulations
Gnomad AFR exome
AF:
0.00126
Gnomad AMR exome
AF:
0.00186
Gnomad ASJ exome
AF:
0.000803
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000196
Gnomad FIN exome
AF:
0.00266
Gnomad NFE exome
AF:
0.00732
Gnomad OTH exome
AF:
0.00455
GnomAD4 exome
AF:
0.00688
AC:
9952
AN:
1447350
Hom.:
54
Cov.:
32
AF XY:
0.00662
AC XY:
4772
AN XY:
720386
show subpopulations
Gnomad4 AFR exome
AF:
0.00108
Gnomad4 AMR exome
AF:
0.00212
Gnomad4 ASJ exome
AF:
0.000727
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000336
Gnomad4 FIN exome
AF:
0.00286
Gnomad4 NFE exome
AF:
0.00840
Gnomad4 OTH exome
AF:
0.00532
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00414
AC:
630
AN:
152252
Hom.:
3
Cov.:
33
AF XY:
0.00386
AC XY:
287
AN XY:
74440
show subpopulations
Gnomad4 AFR
AF:
0.00147
Gnomad4 AMR
AF:
0.00379
Gnomad4 ASJ
AF:
0.000577
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000623
Gnomad4 FIN
AF:
0.00207
Gnomad4 NFE
AF:
0.00701
Gnomad4 OTH
AF:
0.00284
Alfa
AF:
0.00612
Hom.:
0
Bravo
AF:
0.00416
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.00622
EpiControl
AF:
0.00688

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
-0.41
Cadd
Benign
5.5
Dann
Benign
0.61

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs56005919; hg19: chr2-46237530; API