rs973752

Variant names:

• chr17-66432494-C-T
• rs973752
• NM_002737.3:c.206-63707C>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.206-63707C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.845 in 152,084 control chromosomes in the GnomAD database, including 55,120 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 0.84 (55120 hom., cov: 31)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770
• 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]

ENSG00000289587 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCA	NM_002737.3	c.206-63707C>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.206-63707C>T		intron_variant	Intron 2 of 16	1	NM_002737.3	ENSP00000408695.3

Frequencies

GnomAD3 genomes AF: 0.845 AC: 128420 AN: 151964 Hom.: 55087 Cov.: 31

Gnomad AFR AF: 0.683

Gnomad AMI AF: 0.988

Gnomad AMR AF: 0.866

Gnomad ASJ AF: 0.917

Gnomad EAS AF: 0.946

Gnomad SAS AF: 0.959

Gnomad FIN AF: 0.880

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.911

Gnomad OTH AF: 0.871

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

GnomAD4 genome AF: 0.845 AC: 128509 AN: 152084 Hom.: 55120 Cov.: 31 AF XY: 0.849 AC XY: 63078 AN XY: 74324

African (AFR) AF: 0.683 AC: 28323 AN: 41448

American (AMR) AF: 0.866 AC: 13228 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.917 AC: 3185 AN: 3472

East Asian (EAS) AF: 0.945 AC: 4886 AN: 5168

South Asian (SAS) AF: 0.959 AC: 4621 AN: 4818

European-Finnish (FIN) AF: 0.880 AC: 9292 AN: 10564

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.911 AC: 61968 AN: 68016

Other (OTH) AF: 0.873 AC: 1845 AN: 2114

Alfa AF: 0.886 Hom.: 208503

Bravo AF: 0.832

Asia WGS AF: 0.932 AC: 3239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.7
DANN	Benign	0.48
PhyloP100		0.077
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: rs973752; hg19: chr17-64428612;