rs1010544

Positions:

• chr17-66691328-A-G

Variant summary

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

The NM_002737.3(PRKCA):​c.918+2281A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 152,046 control chromosomes in the GnomAD database, including 9,571 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 0.33 (9571 hom., cov: 32)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.21

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKCA	NM_002737.3	c.918+2281A>G		intron_variant		ENST00000413366.8	NP_002728.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKCA	ENST00000413366.8	c.918+2281A>G		intron_variant		1	NM_002737.3	ENSP00000408695	P1
PRKCA	ENST00000578063.5	c.918+2281A>G		intron_variant, NMD_transcript_variant		1		ENSP00000462087
PRKCA	ENST00000284384.6	c.*520+2281A>G		intron_variant, NMD_transcript_variant		5		ENSP00000284384

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49585 AN: 151928 Hom.: 9535 Cov.: 32

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.327 AC: 49669 AN: 152046 Hom.: 9571 Cov.: 32 AF XY: 0.326 AC XY: 24253 AN XY: 74328

Gnomad4 AFR AF: 0.539

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.440

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.224

Gnomad4 OTH AF: 0.292

Alfa AF: 0.257 Hom.: 3070

Bravo AF: 0.339

Asia WGS AF: 0.325 AC: 1129 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.085
DANN	Benign	0.47

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: rs1010544; hg19: chr17-64687446;