NM_002737.3:c.919-20448C>G

Variant names:

• chr17-66712240-C-G
• rs9893009
• NM_002737.3:c.919-20448C>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.919-20448C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 151,960 control chromosomes in the GnomAD database, including 18,934 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 0.49 (18934 hom., cov: 31)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.705
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCA	NM_002737.3	c.919-20448C>G		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.919-20448C>G		intron_variant	Intron 8 of 16	1	NM_002737.3	ENSP00000408695.3
PRKCA	ENST00000284384.6	n.*521-20448C>G		intron_variant	Intron 9 of 14	5		ENSP00000284384.6

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74842 AN: 151842 Hom.: 18898 Cov.: 31

Gnomad AFR AF: 0.588

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.493 AC: 74931 AN: 151960 Hom.: 18934 Cov.: 31 AF XY: 0.494 AC XY: 36711 AN XY: 74296

African (AFR) AF: 0.589 AC: 24395 AN: 41434

American (AMR) AF: 0.460 AC: 7031 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1724 AN: 3472

East Asian (EAS) AF: 0.507 AC: 2615 AN: 5158

South Asian (SAS) AF: 0.406 AC: 1952 AN: 4808

European-Finnish (FIN) AF: 0.520 AC: 5491 AN: 10564

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.442 AC: 30047 AN: 67938

Other (OTH) AF: 0.486 AC: 1026 AN: 2110

Alfa AF: 0.471 Hom.: 2142

Bravo AF: 0.494

Asia WGS AF: 0.445 AC: 1548 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.23
DANN	Benign	0.67
PhyloP100		-0.70
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: rs9893009; hg19: chr17-64708358;