rs732191

Variant names:

• chr17-66353093-G-A
• rs732191
• NM_002737.3:c.205+46966G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002737.3(PRKCA):​c.205+46966G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 151,600 control chromosomes in the GnomAD database, including 23,496 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 0.54 (23496 hom., cov: 31)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.374
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002737.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCA	NM_002737.3	MANE Select	c.205+46966G>A		intron	N/A	NP_002728.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCA	ENST00000413366.8	TSL:1 MANE Select	c.205+46966G>A		intron	N/A	ENSP00000408695.3
	PRKCA	ENST00000578063.5	TSL:1	n.205+46966G>A		intron	N/A	ENSP00000462087.1
	PRKCA	ENST00000284384.6	TSL:5	n.196+46966G>A		intron	N/A	ENSP00000284384.6

Frequencies

GnomAD3 genomes AF: 0.541 AC: 81958 AN: 151480 Hom.: 23491 Cov.: 31

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.565

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

GnomAD4 genome AF: 0.541 AC: 81988 AN: 151600 Hom.: 23496 Cov.: 31 AF XY: 0.540 AC XY: 40010 AN XY: 74058

African (AFR) AF: 0.340 AC: 14091 AN: 41386

American (AMR) AF: 0.526 AC: 8019 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.699 AC: 2425 AN: 3470

East Asian (EAS) AF: 0.457 AC: 2359 AN: 5158

South Asian (SAS) AF: 0.629 AC: 3028 AN: 4812

European-Finnish (FIN) AF: 0.599 AC: 6216 AN: 10384

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.649 AC: 44024 AN: 67822

Other (OTH) AF: 0.567 AC: 1196 AN: 2108

Alfa AF: 0.574 Hom.: 2493

Bravo AF: 0.523

Asia WGS AF: 0.484 AC: 1683 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.0
DANN	Benign	0.61
PhyloP100		0.37
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs732191; hg19: chr17-64349211;