rs9303511

Variant names:

• chr17-66731513-C-T
• rs9303511
• NM_002737.3:c.919-1175C>T

Variant summary

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

The NM_002737.3(PRKCA):​c.919-1175C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 151,926 control chromosomes in the GnomAD database, including 32,868 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 0.66 (32868 hom., cov: 31)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.805
• Publications: 4 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCA	NM_002737.3	c.919-1175C>T		intron_variant	Intron 8 of 16	ENST00000413366.8	NP_002728.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCA	ENST00000413366.8	c.919-1175C>T		intron_variant	Intron 8 of 16	1	NM_002737.3	ENSP00000408695.3
PRKCA	ENST00000284384.6	n.*521-1175C>T		intron_variant	Intron 9 of 14	5		ENSP00000284384.6

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99620 AN: 151808 Hom.: 32814 Cov.: 31

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.694

Gnomad MID AF: 0.622

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.640

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

GnomAD4 genome AF: 0.656 AC: 99733 AN: 151926 Hom.: 32868 Cov.: 31 AF XY: 0.661 AC XY: 49073 AN XY: 74264

African (AFR) AF: 0.686 AC: 28426 AN: 41408

American (AMR) AF: 0.640 AC: 9780 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 2229 AN: 3468

East Asian (EAS) AF: 0.713 AC: 3663 AN: 5136

South Asian (SAS) AF: 0.648 AC: 3120 AN: 4814

European-Finnish (FIN) AF: 0.694 AC: 7329 AN: 10562

Middle Eastern (MID) AF: 0.634 AC: 184 AN: 290

European-Non Finnish (NFE) AF: 0.633 AC: 42982 AN: 67954

Other (OTH) AF: 0.642 AC: 1353 AN: 2106

Alfa AF: 0.638 Hom.: 3839

Bravo AF: 0.653

Asia WGS AF: 0.685 AC: 2384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.1
DANN	Benign	0.56
PhyloP100		0.81
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: rs9303511; hg19: chr17-64727631;