17-66446418-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002737.3(PRKCA):​c.206-49783T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 152,086 control chromosomes in the GnomAD database, including 35,712 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 0.68 ( 35712 hom., cov: 32)

Consequence

PRKCA
NM_002737.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.588
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 Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PRKCANM_002737.3 linkuse as main transcriptc.206-49783T>C intron_variant ENST00000413366.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PRKCAENST00000413366.8 linkuse as main transcriptc.206-49783T>C intron_variant 1 NM_002737.3 P1
PRKCAENST00000578063.5 linkuse as main transcriptc.206-49783T>C intron_variant, NMD_transcript_variant 1
ENST00000689984.2 linkuse as main transcriptn.175-14141A>G intron_variant, non_coding_transcript_variant
PRKCAENST00000284384.6 linkuse as main transcriptc.198-49783T>C intron_variant, NMD_transcript_variant 5

Frequencies

GnomAD3 genomes
AF:
0.684
AC:
103958
AN:
151968
Hom.:
35679
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.692
Gnomad AMI
AF:
0.631
Gnomad AMR
AF:
0.712
Gnomad ASJ
AF:
0.674
Gnomad EAS
AF:
0.714
Gnomad SAS
AF:
0.531
Gnomad FIN
AF:
0.705
Gnomad MID
AF:
0.801
Gnomad NFE
AF:
0.678
Gnomad OTH
AF:
0.718
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.684
AC:
104049
AN:
152086
Hom.:
35712
Cov.:
32
AF XY:
0.685
AC XY:
50902
AN XY:
74306
show subpopulations
Gnomad4 AFR
AF:
0.692
Gnomad4 AMR
AF:
0.712
Gnomad4 ASJ
AF:
0.674
Gnomad4 EAS
AF:
0.713
Gnomad4 SAS
AF:
0.533
Gnomad4 FIN
AF:
0.705
Gnomad4 NFE
AF:
0.678
Gnomad4 OTH
AF:
0.715
Alfa
AF:
0.684
Hom.:
6724
Bravo
AF:
0.691
Asia WGS
AF:
0.615
AC:
2143
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.93
CADD
Benign
1.1
DANN
Benign
0.59

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: rs172939; hg19: chr17-64442536; API