NM_002737.3:c.206-60253A>G

Variant names:

• chr17-66435948-A-G
• rs11079657
• NM_002737.3:c.206-60253A>G

Variant summary

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

The NM_002737.3(PRKCA):​c.206-60253A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 151,916 control chromosomes in the GnomAD database, including 32,621 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 0.64 (32621 hom., cov: 30)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.440
• Publications: 8 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]

ENSG00000289587 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCA	NM_002737.3	c.206-60253A>G		intron_variant	Intron 2 of 16	ENST00000413366.8	NP_002728.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCA	ENST00000413366.8	c.206-60253A>G		intron_variant	Intron 2 of 16	1	NM_002737.3	ENSP00000408695.3

Frequencies

GnomAD3 genomes AF: 0.636 AC: 96562 AN: 151798 Hom.: 32614 Cov.: 30

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.776

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.713

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.768

Gnomad OTH AF: 0.657

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

GnomAD4 genome AF: 0.636 AC: 96586 AN: 151916 Hom.: 32621 Cov.: 30 AF XY: 0.634 AC XY: 47073 AN XY: 74228

African (AFR) AF: 0.400 AC: 16563 AN: 41402

American (AMR) AF: 0.600 AC: 9154 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.776 AC: 2690 AN: 3468

East Asian (EAS) AF: 0.617 AC: 3170 AN: 5138

South Asian (SAS) AF: 0.654 AC: 3146 AN: 4808

European-Finnish (FIN) AF: 0.713 AC: 7516 AN: 10538

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.768 AC: 52217 AN: 67978

Other (OTH) AF: 0.659 AC: 1395 AN: 2116

Alfa AF: 0.726 Hom.: 69148

Bravo AF: 0.615

Asia WGS AF: 0.579 AC: 2013 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.1
DANN	Benign	0.27
PhyloP100		0.44
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: rs11079657; hg19: chr17-64432066;