rs1005651

chr17-66441893-C-Achr17-66441893-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002737.3(PRKCA):c.206-54308C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 151,926 control chromosomes in the GnomAD database, including 35,732 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 (35732 hom., cov: 31)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKCA	NM_002737.3	c.206-54308C>A		intron_variant		ENST00000413366.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCA	ENST00000413366.8	c.206-54308C>A		intron_variant		1	NM_002737.3	P1
PRKCA	ENST00000578063.5	c.206-54308C>A		intron_variant, NMD_transcript_variant		1
	ENST00000689984.2	n.175-9616G>T		intron_variant, non_coding_transcript_variant
PRKCA	ENST00000284384.6	c.198-54308C>A		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.685 AC: 103947 AN: 151808 Hom.: 35705 Cov.: 31

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.625

Gnomad AMR AF: 0.714

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.723

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.799

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.718

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.685 AC: 104030 AN: 151926 Hom.: 35732 Cov.: 31 AF XY: 0.685 AC XY: 50889 AN XY: 74254

Gnomad4 AFR AF: 0.685

Gnomad4 AMR AF: 0.714

Gnomad4 ASJ AF: 0.676

Gnomad4 EAS AF: 0.723

Gnomad4 SAS AF: 0.538

Gnomad4 FIN AF: 0.710

Gnomad4 NFE AF: 0.681

Gnomad4 OTH AF: 0.715

Alfa AF: 0.686 Hom.: 58313

Bravo AF: 0.691

Asia WGS AF: 0.620 AC: 2158 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.23
Dann	Benign	0.49

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

Other links and lift over

dbSNP: rs1005651; hg19: chr17-64438011;