dbSNP rs1042728: PKN1:p.Arg794Arg (chr19-14470251-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_002741.5(PKN1):c.2382A>G(p.Arg794Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0965 in 1,613,816 control chromosomes in the GnomAD database, including 12,509 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 0.18 ( 4248 hom., cov: 32)

Exomes 𝑓: 0.088 ( 8261 hom. )

Consequence

PKN1
NM_002741.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.57

Variant links:

Genes affected

PKN1 (HGNC:9405): (protein kinase N1) The protein encoded by this gene belongs to the protein kinase C superfamily. This kinase is activated by Rho family of small G proteins and may mediate the Rho-dependent signaling pathway. This kinase can be activated by phospholipids and by limited proteolysis. The 3-phosphoinositide dependent protein kinase-1 (PDPK1/PDK1) is reported to phosphorylate this kinase, which may mediate insulin signals to the actin cytoskeleton. The proteolytic activation of this kinase by caspase-3 or related proteases during apoptosis suggests its role in signal transduction related to apoptosis. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

PKN1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP7

Synonymous conserved (PhyloP=-3.57 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKN1	NM_002741.5 link	c.2382A>G	p.Arg794Arg	synonymous_variant	Exon 19 of 22	ENST00000242783.11	NP_002732.3	Q16512-1
PKN1	NM_213560.3 link	c.2400A>G	p.Arg800Arg	synonymous_variant	Exon 19 of 22		NP_998725.1	Q16512-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKN1	ENST00000242783.11 link	c.2382A>G	p.Arg794Arg	synonymous_variant	Exon 19 of 22	1	NM_002741.5	ENSP00000242783.7		Q16512-1

Frequencies

GnomAD3 genomes

AF:

0.180

AC:

27313

AN:

151904

Hom.:

4229

Cov.:

show subpopulations

Gnomad AFR

AF:

0.425

Gnomad AMI

AF:

0.109

Gnomad AMR

AF:

0.154

Gnomad ASJ

AF:

0.0444

Gnomad EAS

AF:

0.106

Gnomad SAS

AF:

0.0812

Gnomad FIN

AF:

0.0816

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0738

Gnomad OTH

AF:

0.159

GnomAD3 exomes

AF:

0.113

AC:

28348

AN:

251064

Hom.:

2688

AF XY:

0.103

AC XY:

14024

AN XY:

135776

show subpopulations

Gnomad AFR exome

AF:

0.436

Gnomad AMR exome

AF:

0.164

Gnomad ASJ exome

AF:

0.0516

Gnomad EAS exome

AF:

0.105

Gnomad SAS exome

AF:

0.0804

Gnomad FIN exome

AF:

0.0857

Gnomad NFE exome

AF:

0.0729

Gnomad OTH exome

AF:

0.0944

GnomAD4 exome

AF:

0.0878

AC:

128370

AN:

1461794

Hom.:

8261

Cov.:

AF XY:

0.0860

AC XY:

62550

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.438

Gnomad4 AMR exome

AF:

0.163

Gnomad4 ASJ exome

AF:

0.0518

Gnomad4 EAS exome

AF:

0.0922

Gnomad4 SAS exome

AF:

0.0821

Gnomad4 FIN exome

AF:

0.0854

Gnomad4 NFE exome

AF:

0.0749

Gnomad4 OTH exome

AF:

0.0998

GnomAD4 genome

AF:

0.180

AC:

27367

AN:

152022

Hom.:

4248

Cov.:

AF XY:

0.179

AC XY:

13326

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.425

Gnomad4 AMR

AF:

0.154

Gnomad4 ASJ

AF:

0.0444

Gnomad4 EAS

AF:

0.105

Gnomad4 SAS

AF:

0.0802

Gnomad4 FIN

AF:

0.0816

Gnomad4 NFE

AF:

0.0738

Gnomad4 OTH

AF:

0.158

Alfa

AF:

0.110

Hom.:

1522

Bravo

AF:

0.197

Asia WGS

AF:

0.123

AC:

429

AN:

3478

EpiCase

AF:

0.0703

EpiControl

AF:

0.0698

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.4

DANN

Benign

0.53

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

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