rs1985633

Variant names:

• chr17-66635635-A-C
• rs1985633
• NM_002737.3:c.289-5720A>C

Variant summary

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

The NM_002737.3(PRKCA):​c.289-5720A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 152,120 control chromosomes in the GnomAD database, including 30,099 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 0.63 (30099 hom., cov: 33)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.781
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCA	NM_002737.3	c.289-5720A>C		intron_variant	Intron 3 of 16	ENST00000413366.8	NP_002728.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCA	ENST00000413366.8	c.289-5720A>C		intron_variant	Intron 3 of 16	1	NM_002737.3	ENSP00000408695.3
PRKCA	ENST00000578063.5	n.289-5720A>C		intron_variant	Intron 3 of 9	1		ENSP00000462087.1
PRKCA	ENST00000284384.6	n.341-5720A>C		intron_variant	Intron 4 of 14	5		ENSP00000284384.6

Frequencies

GnomAD3 genomes AF: 0.628 AC: 95462 AN: 152002 Hom.: 30063 Cov.: 33

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.609

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

GnomAD4 genome AF: 0.628 AC: 95553 AN: 152120 Hom.: 30099 Cov.: 33 AF XY: 0.628 AC XY: 46717 AN XY: 74348

African (AFR) AF: 0.699 AC: 28992 AN: 41498

American (AMR) AF: 0.629 AC: 9614 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.668 AC: 2321 AN: 3472

East Asian (EAS) AF: 0.552 AC: 2855 AN: 5174

South Asian (SAS) AF: 0.581 AC: 2797 AN: 4818

European-Finnish (FIN) AF: 0.624 AC: 6599 AN: 10574

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.593 AC: 40291 AN: 67984

Other (OTH) AF: 0.613 AC: 1294 AN: 2112

Alfa AF: 0.604 Hom.: 5851

Bravo AF: 0.631

Asia WGS AF: 0.589 AC: 2047 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.9
DANN	Benign	0.78
PhyloP100		-0.78
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: rs1985633; hg19: chr17-64631753;