chr17-66806426-C-T

Position:

• chr17-66806426-C-T

Variant summary

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

The NM_002737.3(PRKCA):​c.*2389C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 152,022 control chromosomes in the GnomAD database, including 12,157 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 0.39 (12142 hom., cov: 31)
  • Exomes 𝑓: 0.45 (15 hom.)
• Consequence: PRKCA NM_002737.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.218

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKCA	NM_002737.3	c.*2389C>T		3_prime_UTR_variant	17/17	ENST00000413366.8	NP_002728.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKCA	ENST00000413366.8	c.*2389C>T		3_prime_UTR_variant	17/17	1	NM_002737.3	ENSP00000408695.3

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59843 AN: 151770 Hom.: 12137 Cov.: 31

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.611

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.365

GnomAD4 exome AF: 0.449 AC: 61 AN: 136 Hom.: 15 Cov.: 0 AF XY: 0.462 AC XY: 48 AN XY: 104

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.667

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.446

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.394 AC: 59872 AN: 151886 Hom.: 12142 Cov.: 31 AF XY: 0.401 AC XY: 29767 AN XY: 74222

Gnomad4 AFR AF: 0.396

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.279

Gnomad4 EAS AF: 0.611

Gnomad4 SAS AF: 0.453

Gnomad4 FIN AF: 0.508

Gnomad4 NFE AF: 0.370

Gnomad4 OTH AF: 0.364

Alfa AF: 0.363 Hom.: 13470

Bravo AF: 0.382

Asia WGS AF: 0.498 AC: 1731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.1
DANN	Benign	0.49

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: rs7342847; hg19: chr17-64802544;