17-66788327-C-T

Variant names:

• chr17-66788327-C-T
• rs9896575
• NM_002737.3:c.1714-512C>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.1714-512C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,018 control chromosomes in the GnomAD database, including 3,456 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 0.17 (3456 hom., cov: 32)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCA	NM_002737.3	c.1714-512C>T		intron_variant	Intron 15 of 16	ENST00000413366.8	NP_002728.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCA	ENST00000413366.8	c.1714-512C>T		intron_variant	Intron 15 of 16	1	NM_002737.3	ENSP00000408695.3

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25344 AN: 151900 Hom.: 3441 Cov.: 32

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.0593

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.0725

Gnomad FIN AF: 0.0480

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0775

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.167 AC: 25403 AN: 152018 Hom.: 3456 Cov.: 32 AF XY: 0.164 AC XY: 12197 AN XY: 74314

African (AFR) AF: 0.373 AC: 15449 AN: 41424

American (AMR) AF: 0.141 AC: 2158 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 371 AN: 3470

East Asian (EAS) AF: 0.180 AC: 929 AN: 5168

South Asian (SAS) AF: 0.0722 AC: 347 AN: 4808

European-Finnish (FIN) AF: 0.0480 AC: 509 AN: 10594

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0775 AC: 5264 AN: 67960

Other (OTH) AF: 0.141 AC: 297 AN: 2112

Alfa AF: 0.0807 Hom.: 457

Bravo AF: 0.184

Asia WGS AF: 0.142 AC: 494 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.17
DANN	Benign	0.66
PhyloP100		-1.8
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

Publications

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Other links and lift over

dbSNP: rs9896575; hg19: chr17-64784445;