Genetic Variant PRKCA:n.-5_-4dupGG (chr17-66302841-T-TGG) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_002737.3(PRKCA):c.-5_-4dupGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0171 in 1,576,378 control chromosomes in the GnomAD database, including 255 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.012 ( 17 hom., cov: 30)

Exomes 𝑓: 0.018 ( 238 hom. )

Consequence

PRKCA
NM_002737.3 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0800

Publications

2 publications found

Variant links:

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]

PRKCA links:

ENSG00000307784 (HGNC:):

ENSG00000307784 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0123 (1852/151160) while in subpopulation NFE AF = 0.0208 (1407/67696). AF 95% confidence interval is 0.0199. There are 17 homozygotes in GnomAd4. There are 866 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.

BS2

High AC in GnomAd4 at 1852 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCA	NM_002737.3 link	c.-5_-4dupGG		5_prime_UTR_variant	Exon 1 of 17	ENST00000413366.8	NP_002728.2	P17252L7RSM7Q7Z727

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCA	ENST00000413366.8 link	c.-5_-4dupGG		5_prime_UTR_variant	Exon 1 of 17	1	NM_002737.3	ENSP00000408695.3		P17252

Frequencies

GnomAD3 genomes

AF:

0.0123

AC:

1853

AN:

151048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00395

Gnomad AMI

AF:

0.0220

Gnomad AMR

AF:

0.00743

Gnomad ASJ

AF:

0.000578

Gnomad EAS

AF:

0.000785

Gnomad SAS

AF:

0.00791

Gnomad FIN

AF:

0.00917

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0208

Gnomad OTH

AF:

0.00530

GnomAD2 exomes

AF:

0.0119

AC:

2473

AN:

208084

AF XY:

0.0120

show subpopulations

Gnomad AFR exome

AF:

0.00315

Gnomad AMR exome

AF:

0.00510

Gnomad ASJ exome

AF:

0.00135

Gnomad EAS exome

AF:

0.000698

Gnomad FIN exome

AF:

0.00982

Gnomad NFE exome

AF:

0.0198

Gnomad OTH exome

AF:

0.0120

GnomAD4 exome

AF:

0.0176

AC:

25149

AN:

1425218

Hom.:

238

Cov.:

AF XY:

0.0172

AC XY:

12177

AN XY:

707972

show subpopulations

African (AFR)

AF:

0.00316

AC:

AN:

30990

American (AMR)

AF:

0.00478

AC:

195

AN:

40776

Ashkenazi Jewish (ASJ)

AF:

0.000921

AC:

AN:

24964

East Asian (EAS)

AF:

0.00104

AC:

AN:

36408

South Asian (SAS)

AF:

0.00746

AC:

619

AN:

82982

European-Finnish (FIN)

AF:

0.0102

AC:

521

AN:

51260

Middle Eastern (MID)

AF:

0.00637

AC:

AN:

5650

European-Non Finnish (NFE)

AF:

0.0209

AC:

22906

AN:

1093444

Other (OTH)

AF:

0.0121

AC:

713

AN:

58744

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

1149

2299

3448

4598

5747

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0123

AC:

1852

AN:

151160

Hom.:

Cov.:

AF XY:

0.0117

AC XY:

866

AN XY:

73870

show subpopulations

African (AFR)

AF:

0.00394

AC:

163

AN:

41362

American (AMR)

AF:

0.00742

AC:

113

AN:

15220

Ashkenazi Jewish (ASJ)

AF:

0.000578

AC:

AN:

3460

East Asian (EAS)

AF:

0.000788

AC:

AN:

5078

South Asian (SAS)

AF:

0.00791

AC:

AN:

4802

European-Finnish (FIN)

AF:

0.00917

AC:

AN:

10246

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0208

AC:

1407

AN:

67696

Other (OTH)

AF:

0.00525

AC:

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

195

292

390

487

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00529

Hom.:

112

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.080

Mutation Taster

=300/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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chr17-66302841-T-TGG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over