17-66302958-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000413366.8(PRKCA):​c.107A>G​(p.Asp36Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D36E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

PRKCA
ENST00000413366.8 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.18
Variant links:
Genes affected
PRKCA (HGNC:9393): (protein kinase C alpha) 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 reported to play roles in many different cellular processes, such as cell adhesion, cell transformation, cell cycle checkpoint, and cell volume control. Knockout studies in mice suggest that this kinase may be a fundamental regulator of cardiac contractility and Ca(2+) handling in myocytes. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.37640435).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PRKCANM_002737.3 linkuse as main transcriptc.107A>G p.Asp36Gly missense_variant 1/17 ENST00000413366.8 NP_002728.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PRKCAENST00000413366.8 linkuse as main transcriptc.107A>G p.Asp36Gly missense_variant 1/171 NM_002737.3 ENSP00000408695 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenApr 01, 2024PRKCA: PM2, PP2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
0.0016
T
BayesDel_noAF
Benign
-0.24
CADD
Uncertain
25
DANN
Benign
0.88
DEOGEN2
Benign
0.30
T
Eigen
Benign
-0.80
Eigen_PC
Benign
-0.70
FATHMM_MKL
Uncertain
0.82
D
LIST_S2
Benign
0.60
T
M_CAP
Pathogenic
0.79
D
MetaRNN
Benign
0.38
T
MetaSVM
Benign
-0.79
T
MutationAssessor
Benign
1.3
L
MutationTaster
Benign
0.93
D
PrimateAI
Uncertain
0.74
T
PROVEAN
Benign
-0.60
N
REVEL
Benign
0.28
Sift
Benign
1.0
T
Sift4G
Benign
1.0
T
Polyphen
0.0
B
Vest4
0.28
MutPred
0.52
Gain of MoRF binding (P = 0.0346);
MVP
0.76
MPC
1.7
ClinPred
0.19
T
GERP RS
2.3
Varity_R
0.21
gMVP
0.84

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-64299076; API