17-66688447-C-T

Variant names:

• chr17-66688447-C-T
• rs1010546
• NM_002737.3:c.821+11C>T

Variant summary

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

The NM_002737.3(PRKCA):​c.821+11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 1,613,594 control chromosomes in the GnomAD database, including 15,375 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 0.12 (1175 hom., cov: 32)
  • Exomes 𝑓: 0.14 (14200 hom.)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0720
• Publications: 14 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCA	NM_002737.3	c.821+11C>T		intron_variant	Intron 7 of 16	ENST00000413366.8	NP_002728.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCA	ENST00000413366.8	c.821+11C>T		intron_variant	Intron 7 of 16	1	NM_002737.3	ENSP00000408695.3
PRKCA	ENST00000578063.5	n.821+11C>T		intron_variant	Intron 7 of 9	1		ENSP00000462087.1
PRKCA	ENST00000284384.6	n.*423+11C>T		intron_variant	Intron 8 of 14	5		ENSP00000284384.6

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18039 AN: 151958 Hom.: 1178 Cov.: 32

Gnomad AFR AF: 0.0705

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.0549

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.130

GnomAD2 exomes AF: 0.138 AC: 34643 AN: 251120 AF XY: 0.142

Gnomad AFR exome AF: 0.0685

Gnomad AMR exome AF: 0.151

Gnomad ASJ exome AF: 0.177

Gnomad EAS exome AF: 0.0606

Gnomad FIN exome AF: 0.157

Gnomad NFE exome AF: 0.137

Gnomad OTH exome AF: 0.140

GnomAD4 exome AF: 0.135 AC: 197890 AN: 1461518 Hom.: 14200 Cov.: 32 AF XY: 0.137 AC XY: 99551 AN XY: 727070

African (AFR) AF: 0.0677 AC: 2266 AN: 33474

American (AMR) AF: 0.151 AC: 6774 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 4650 AN: 26120

East Asian (EAS) AF: 0.0548 AC: 2174 AN: 39692

South Asian (SAS) AF: 0.185 AC: 15947 AN: 86226

European-Finnish (FIN) AF: 0.153 AC: 8183 AN: 53406

Middle Eastern (MID) AF: 0.180 AC: 1037 AN: 5758

European-Non Finnish (NFE) AF: 0.134 AC: 148801 AN: 1111752

Other (OTH) AF: 0.133 AC: 8058 AN: 60376

GnomAD4 genome AF: 0.119 AC: 18041 AN: 152076 Hom.: 1175 Cov.: 32 AF XY: 0.122 AC XY: 9065 AN XY: 74318

African (AFR) AF: 0.0703 AC: 2916 AN: 41476

American (AMR) AF: 0.136 AC: 2081 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 596 AN: 3470

East Asian (EAS) AF: 0.0547 AC: 283 AN: 5178

South Asian (SAS) AF: 0.178 AC: 853 AN: 4800

European-Finnish (FIN) AF: 0.159 AC: 1675 AN: 10564

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9251 AN: 67988

Other (OTH) AF: 0.130 AC: 274 AN: 2108

Alfa AF: 0.133 Hom.: 2593

Bravo AF: 0.114

Asia WGS AF: 0.128 AC: 445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.4
DANN	Benign	0.65
PhyloP100		0.072
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1010546; hg19: chr17-64684565;