chr17-66780023-C-T

Variant names:

• chr17-66780023-C-T
• rs9896905
• NM_002737.3:c.1605+5956C>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.1605+5956C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0914 in 152,214 control chromosomes in the GnomAD database, including 773 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 0.091 (773 hom., cov: 32)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26
• Publications: 5 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCA	NM_002737.3	c.1605+5956C>T		intron_variant	Intron 14 of 16	ENST00000413366.8	NP_002728.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCA	ENST00000413366.8	c.1605+5956C>T		intron_variant	Intron 14 of 16	1	NM_002737.3	ENSP00000408695.3

Frequencies

GnomAD3 genomes AF: 0.0913 AC: 13881 AN: 152094 Hom.: 769 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0672

Gnomad ASJ AF: 0.0767

Gnomad EAS AF: 0.0483

Gnomad SAS AF: 0.0648

Gnomad FIN AF: 0.0454

Gnomad MID AF: 0.0510

Gnomad NFE AF: 0.0736

Gnomad OTH AF: 0.0824

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

GnomAD4 genome AF: 0.0914 AC: 13914 AN: 152214 Hom.: 773 Cov.: 32 AF XY: 0.0900 AC XY: 6697 AN XY: 74416

African (AFR) AF: 0.152 AC: 6328 AN: 41518

American (AMR) AF: 0.0672 AC: 1028 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0767 AC: 266 AN: 3468

East Asian (EAS) AF: 0.0480 AC: 249 AN: 5184

South Asian (SAS) AF: 0.0652 AC: 314 AN: 4814

European-Finnish (FIN) AF: 0.0454 AC: 481 AN: 10604

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0736 AC: 5005 AN: 68012

Other (OTH) AF: 0.0820 AC: 173 AN: 2110

Alfa AF: 0.0812 Hom.: 83

Bravo AF: 0.0965

Asia WGS AF: 0.0670 AC: 235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.7
DANN	Benign	0.83
PhyloP100		1.3
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: rs9896905; hg19: chr17-64776141;