dbSNP rs55683301: PRKCI:p.Arg327Arg (chr3-170281882-A-G) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_002740.6(PRKCI):c.981A>G(p.Arg327Arg) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0195 in 1,587,912 control chromosomes in the GnomAD database, including 430 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.015 ( 41 hom., cov: 32)

Exomes 𝑓: 0.020 ( 389 hom. )

Consequence

PRKCI
NM_002740.6 splice_region, synonymous

Scores

Splicing: ADA: 0.000002493

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0710

Variant links:

Genes affected

PRKCI (HGNC:9404): (protein kinase C iota) This gene encodes a member of the protein kinase C (PKC) family of serine/threonine protein kinases. The PKC family comprises at least eight members, which are differentially expressed and are involved in a wide variety of cellular processes. This protein kinase is calcium-independent and phospholipid-dependent. It is not activated by phorbolesters or diacylglycerol. This kinase can be recruited to vesicle tubular clusters (VTCs) by direct interaction with the small GTPase RAB2, where this kinase phosphorylates glyceraldehyde-3-phosphate dehydrogenase (GAPD/GAPDH) and plays a role in microtubule dynamics in the early secretory pathway. This kinase is found to be necessary for BCL-ABL-mediated resistance to drug-induced apoptosis and therefore protects leukemia cells against drug-induced apoptosis. There is a single exon pseudogene mapped on chromosome X. [provided by RefSeq, Jul 2008]

PRKCI links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP7

Synonymous conserved (PhyloP=0.071 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCI	NM_002740.6 link	c.981A>G	p.Arg327Arg	splice_region_variant, synonymous_variant	Exon 11 of 18	ENST00000295797.5	NP_002731.4	P41743
PRKCI	XM_047448575.1 link	c.639A>G	p.Arg213Arg	splice_region_variant, synonymous_variant	Exon 10 of 17		XP_047304531.1
PRKCI	XM_047448574.1 link	c.981A>G	p.Arg327Arg	splice_region_variant, synonymous_variant	Exon 11 of 13		XP_047304530.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCI	ENST00000295797.5 link	c.981A>G	p.Arg327Arg	splice_region_variant, synonymous_variant	Exon 11 of 18	1	NM_002740.6	ENSP00000295797.4		P41743
PRKCI	ENST00000482353.2 link	n.273A>G		non_coding_transcript_exon_variant	Exon 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.0155

AC:

2359

AN:

152046

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00413

Gnomad AMI

AF:

0.109

Gnomad AMR

AF:

0.00668

Gnomad ASJ

AF:

0.0208

Gnomad EAS

AF:

0.0853

Gnomad SAS

AF:

0.00456

Gnomad FIN

AF:

0.0116

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0190

Gnomad OTH

AF:

0.0158

GnomAD3 exomes

AF:

0.0187

AC:

4332

AN:

231652

Hom.:

105

AF XY:

0.0182

AC XY:

2278

AN XY:

125376

show subpopulations

Gnomad AFR exome

AF:

0.00449

Gnomad AMR exome

AF:

0.00507

Gnomad ASJ exome

AF:

0.0178

Gnomad EAS exome

AF:

0.0898

Gnomad SAS exome

AF:

0.00460

Gnomad FIN exome

AF:

0.00836

Gnomad NFE exome

AF:

0.0190

Gnomad OTH exome

AF:

0.0154

GnomAD4 exome

AF:

0.0199

AC:

28572

AN:

1435748

Hom.:

389

Cov.:

AF XY:

0.0193

AC XY:

13796

AN XY:

713520

show subpopulations

Gnomad4 AFR exome

AF:

0.00317

Gnomad4 AMR exome

AF:

0.00535

Gnomad4 ASJ exome

AF:

0.0166

Gnomad4 EAS exome

AF:

0.0768

Gnomad4 SAS exome

AF:

0.00489

Gnomad4 FIN exome

AF:

0.00880

Gnomad4 NFE exome

AF:

0.0207

Gnomad4 OTH exome

AF:

0.0196

GnomAD4 genome

AF:

0.0155

AC:

2358

AN:

152164

Hom.:

Cov.:

AF XY:

0.0149

AC XY:

1110

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.00412

Gnomad4 AMR

AF:

0.00668

Gnomad4 ASJ

AF:

0.0208

Gnomad4 EAS

AF:

0.0853

Gnomad4 SAS

AF:

0.00456

Gnomad4 FIN

AF:

0.0116

Gnomad4 NFE

AF:

0.0190

Gnomad4 OTH

AF:

0.0156

Alfa

AF:

0.0207

Hom.:

Bravo

AF:

0.0154

Asia WGS

AF:

0.0350

AC:

122

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

8.1

DANN

Benign

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0000025

dbscSNV1_RF

Benign

0.014

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over