17-66322239-G-C

Variant names:

• chr17-66322239-G-C
• rs9912468
• NM_002737.3:c.205+16112G>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.205+16112G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 151,936 control chromosomes in the GnomAD database, including 26,433 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 0.59 (26433 hom., cov: 31)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.134
• Publications: 36 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.619 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.205+16112G>C		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.205+16112G>C		intron	N/A	ENSP00000408695.3
	PRKCA	ENST00000578063.5	TSL:1	n.205+16112G>C		intron	N/A	ENSP00000462087.1
	PRKCA	ENST00000284384.6	TSL:5	n.196+16112G>C		intron	N/A	ENSP00000284384.6

Frequencies

GnomAD3 genomes AF: 0.589 AC: 89383 AN: 151818 Hom.: 26390 Cov.: 31

Gnomad AFR AF: 0.623

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.638

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.526

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

GnomAD4 genome AF: 0.589 AC: 89485 AN: 151936 Hom.: 26433 Cov.: 31 AF XY: 0.589 AC XY: 43766 AN XY: 74274

African (AFR) AF: 0.624 AC: 25826 AN: 41402

American (AMR) AF: 0.585 AC: 8941 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 1616 AN: 3468

East Asian (EAS) AF: 0.570 AC: 2944 AN: 5168

South Asian (SAS) AF: 0.638 AC: 3070 AN: 4814

European-Finnish (FIN) AF: 0.574 AC: 6055 AN: 10554

Middle Eastern (MID) AF: 0.418 AC: 122 AN: 292

European-Non Finnish (NFE) AF: 0.578 AC: 39241 AN: 67938

Other (OTH) AF: 0.530 AC: 1121 AN: 2114

Alfa AF: 0.560 Hom.: 11775

Bravo AF: 0.588

Asia WGS AF: 0.617 AC: 2143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.41
PhyloP100		0.13
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: rs9912468; hg19: chr17-64318357;