17-66466442-G-A

Variant names:

• chr17-66466442-G-A
• rs3848426
• NM_002737.3:c.206-29759G>A

Variant summary

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

The NM_002737.3(PRKCA):​c.206-29759G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 152,032 control chromosomes in the GnomAD database, including 7,035 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 0.30 (7035 hom., cov: 32)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.395
• Publications: 7 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002737.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCA	NM_002737.3	MANE Select	c.206-29759G>A		intron	N/A	NP_002728.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCA	ENST00000413366.8	TSL:1 MANE Select	c.206-29759G>A		intron	N/A	ENSP00000408695.3
	PRKCA	ENST00000578063.5	TSL:1	n.206-29759G>A		intron	N/A	ENSP00000462087.1
	PRKCA	ENST00000284384.6	TSL:5	n.197-29759G>A		intron	N/A	ENSP00000284384.6

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45192 AN: 151914 Hom.: 7034 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.356

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

GnomAD4 genome AF: 0.297 AC: 45213 AN: 152032 Hom.: 7035 Cov.: 32 AF XY: 0.300 AC XY: 22302 AN XY: 74308

African (AFR) AF: 0.202 AC: 8371 AN: 41480

American (AMR) AF: 0.325 AC: 4963 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1285 AN: 3468

East Asian (EAS) AF: 0.285 AC: 1470 AN: 5162

South Asian (SAS) AF: 0.314 AC: 1510 AN: 4810

European-Finnish (FIN) AF: 0.376 AC: 3969 AN: 10550

Middle Eastern (MID) AF: 0.435 AC: 127 AN: 292

European-Non Finnish (NFE) AF: 0.331 AC: 22477 AN: 67964

Other (OTH) AF: 0.357 AC: 755 AN: 2112

Alfa AF: 0.321 Hom.: 4223

Bravo AF: 0.292

Asia WGS AF: 0.287 AC: 1000 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.6
DANN	Benign	0.82
PhyloP100		-0.40
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: rs3848426; hg19: chr17-64462560;