rs3803820

Positions:

• chr17-66742179-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002737.3(PRKCA):​c.1386-443A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,242 control chromosomes in the GnomAD database, including 2,505 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 0.15 (2505 hom., cov: 32)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.227

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKCA	NM_002737.3	c.1386-443A>G		intron_variant		ENST00000413366.8	NP_002728.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKCA	ENST00000413366.8	c.1386-443A>G		intron_variant		1	NM_002737.3	ENSP00000408695	P1
PRKCA	ENST00000284384.6	c.*988-443A>G		intron_variant, NMD_transcript_variant		5		ENSP00000284384

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22307 AN: 152124 Hom.: 2487 Cov.: 32

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.0778

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.0385

Gnomad FIN AF: 0.0864

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0737

Gnomad OTH AF: 0.145

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

GnomAD4 genome AF: 0.147 AC: 22368 AN: 152242 Hom.: 2505 Cov.: 32 AF XY: 0.145 AC XY: 10825 AN XY: 74436

Gnomad4 AFR AF: 0.312

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.0778

Gnomad4 EAS AF: 0.132

Gnomad4 SAS AF: 0.0379

Gnomad4 FIN AF: 0.0864

Gnomad4 NFE AF: 0.0737

Gnomad4 OTH AF: 0.144

Alfa AF: 0.0912 Hom.: 805

Bravo AF: 0.158

Asia WGS AF: 0.0920 AC: 319 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.1
DANN	Benign	0.48

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

LitVar

Other links and lift over

dbSNP: rs3803820; hg19: chr17-64738297;