17-66336444-C-T

Variant names:

• chr17-66336444-C-T
• rs7218425
• NM_002737.3:c.205+30317C>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.205+30317C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.677 in 152,020 control chromosomes in the GnomAD database, including 35,911 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 0.68 (35911 hom., cov: 31)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00300
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCA	NM_002737.3	c.205+30317C>T		intron_variant	Intron 2 of 16	ENST00000413366.8	NP_002728.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCA	ENST00000413366.8	c.205+30317C>T		intron_variant	Intron 2 of 16	1	NM_002737.3	ENSP00000408695.3
PRKCA	ENST00000578063.5	n.205+30317C>T		intron_variant	Intron 2 of 9	1		ENSP00000462087.1
PRKCA	ENST00000284384.6	n.196+30317C>T		intron_variant	Intron 2 of 14	5		ENSP00000284384.6
PRKCA	ENST00000583361.1	n.250-3347C>T		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.677 AC: 102804 AN: 151900 Hom.: 35901 Cov.: 31

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.761

Gnomad AMR AF: 0.710

Gnomad ASJ AF: 0.865

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.785

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.764

Gnomad OTH AF: 0.717

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

GnomAD4 genome AF: 0.677 AC: 102849 AN: 152020 Hom.: 35911 Cov.: 31 AF XY: 0.677 AC XY: 50330 AN XY: 74312

African (AFR) AF: 0.484 AC: 20031 AN: 41426

American (AMR) AF: 0.710 AC: 10845 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.865 AC: 3003 AN: 3470

East Asian (EAS) AF: 0.560 AC: 2887 AN: 5156

South Asian (SAS) AF: 0.707 AC: 3407 AN: 4816

European-Finnish (FIN) AF: 0.785 AC: 8289 AN: 10560

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.764 AC: 51956 AN: 67992

Other (OTH) AF: 0.716 AC: 1514 AN: 2116

Alfa AF: 0.721 Hom.: 64590

Bravo AF: 0.669

Asia WGS AF: 0.613 AC: 2132 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.0
DANN	Benign	0.82
PhyloP100		0.0030
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: rs7218425; hg19: chr17-64332562;