rs1003425

Variant names:

• chr17-66556781-A-G
• rs1003425
• NM_002737.3:c.288+60498A>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.288+60498A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 151,966 control chromosomes in the GnomAD database, including 9,027 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 (9027 hom., cov: 31)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.66
• 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=-1.07).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCA	NM_002737.3	c.288+60498A>G		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.288+60498A>G		intron_variant	Intron 3 of 16	1	NM_002737.3	ENSP00000408695.3
PRKCA	ENST00000578063.5	n.288+60498A>G		intron_variant	Intron 3 of 9	1		ENSP00000462087.1
PRKCA	ENST00000284384.6	n.340+2202A>G		intron_variant	Intron 4 of 14	5		ENSP00000284384.6

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51564 AN: 151848 Hom.: 9014 Cov.: 31

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.340 AC: 51624 AN: 151966 Hom.: 9027 Cov.: 31 AF XY: 0.341 AC XY: 25311 AN XY: 74284

African (AFR) AF: 0.407 AC: 16854 AN: 41408

American (AMR) AF: 0.355 AC: 5425 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1288 AN: 3462

East Asian (EAS) AF: 0.225 AC: 1158 AN: 5156

South Asian (SAS) AF: 0.437 AC: 2106 AN: 4816

European-Finnish (FIN) AF: 0.267 AC: 2829 AN: 10586

Middle Eastern (MID) AF: 0.404 AC: 118 AN: 292

European-Non Finnish (NFE) AF: 0.308 AC: 20936 AN: 67962

Other (OTH) AF: 0.339 AC: 713 AN: 2106

Alfa AF: 0.330 Hom.: 1028

Bravo AF: 0.346

Asia WGS AF: 0.342 AC: 1191 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.20
DANN	Benign	0.19
PhyloP100		-2.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1003425; hg19: chr17-64552899;