17-66521195-T-A

Variant names:

• chr17-66521195-T-A
• rs11651708
• NM_002737.3:c.288+24912T>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.288+24912T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 152,086 control chromosomes in the GnomAD database, including 8,926 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 0.34 (8926 hom., cov: 33)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.571
• Publications: 12 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 (SAS) allele frequency at 95% confidence interval = 0.476 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.288+24912T>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.288+24912T>A		intron	N/A	ENSP00000408695.3
	PRKCA	ENST00000578063.5	TSL:1	n.288+24912T>A		intron	N/A	ENSP00000462087.1
	PRKCA	ENST00000284384.6	TSL:5	n.279+24912T>A		intron	N/A	ENSP00000284384.6

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51582 AN: 151968 Hom.: 8919 Cov.: 33

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.302

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

GnomAD4 genome AF: 0.339 AC: 51622 AN: 152086 Hom.: 8926 Cov.: 33 AF XY: 0.339 AC XY: 25231 AN XY: 74364

African (AFR) AF: 0.334 AC: 13848 AN: 41476

American (AMR) AF: 0.305 AC: 4659 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1148 AN: 3472

East Asian (EAS) AF: 0.456 AC: 2358 AN: 5166

South Asian (SAS) AF: 0.493 AC: 2376 AN: 4820

European-Finnish (FIN) AF: 0.313 AC: 3300 AN: 10560

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22872 AN: 67986

Other (OTH) AF: 0.306 AC: 644 AN: 2108

Alfa AF: 0.187 Hom.: 394

Bravo AF: 0.335

Asia WGS AF: 0.468 AC: 1626 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	12
DANN	Benign	0.54
PhyloP100		0.57
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: rs11651708; hg19: chr17-64517313;