17-66539761-C-T

Variant names:

• chr17-66539761-C-T
• rs2361486
• NM_002737.3:c.288+43478C>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.288+43478C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,124 control chromosomes in the GnomAD database, including 1,828 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 0.14 (1828 hom., cov: 32)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.201
• Publications: 7 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 = 0.183 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCA	NM_002737.3	MANE Select	c.288+43478C>T		intron	N/A	NP_002728.2	L7RSM7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCA	ENST00000413366.8	TSL:1 MANE Select	c.288+43478C>T		intron	N/A	ENSP00000408695.3	P17252
	PRKCA	ENST00000578063.5	TSL:1	n.288+43478C>T		intron	N/A	ENSP00000462087.1	J3KRN5
	PRKCA	ENST00000882063.1		c.288+43478C>T		intron	N/A	ENSP00000552122.1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21949 AN: 152006 Hom.: 1827 Cov.: 32

Gnomad AFR AF: 0.0752

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.171

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

GnomAD4 genome AF: 0.144 AC: 21965 AN: 152124 Hom.: 1828 Cov.: 32 AF XY: 0.146 AC XY: 10866 AN XY: 74374

African (AFR) AF: 0.0752 AC: 3120 AN: 41516

American (AMR) AF: 0.189 AC: 2888 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 821 AN: 3470

East Asian (EAS) AF: 0.191 AC: 985 AN: 5170

South Asian (SAS) AF: 0.150 AC: 723 AN: 4812

European-Finnish (FIN) AF: 0.188 AC: 1988 AN: 10580

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10857 AN: 67996

Other (OTH) AF: 0.172 AC: 363 AN: 2106

Alfa AF: 0.159 Hom.: 5399

Bravo AF: 0.146

Asia WGS AF: 0.165 AC: 577 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.2
DANN	Benign	0.80
PhyloP100		-0.20
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: rs2361486; hg19: chr17-64535879;