rs1042728

Variant names:

• chr19-14470251-A-G
• rs1042728
• NM_002741.5:c.2382A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.57
• Publications: 25 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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	c.2382A>G	p.Arg794Arg	synonymous_variant	Exon 19 of 22	ENST00000242783.11	NP_002732.3
PKN1	NM_213560.3	c.2400A>G	p.Arg800Arg	synonymous_variant	Exon 19 of 22		NP_998725.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27313 AN: 151904 Hom.: 4229 Cov.: 32

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

GnomAD2 exomes AF: 0.113 AC: 28348 AN: 251064 AF XY: 0.103

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 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.: 33 AF XY: 0.0860 AC XY: 62550 AN XY: 727206

African (AFR) AF: 0.438 AC: 14648 AN: 33474

American (AMR) AF: 0.163 AC: 7278 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0518 AC: 1355 AN: 26134

East Asian (EAS) AF: 0.0922 AC: 3659 AN: 39700

South Asian (SAS) AF: 0.0821 AC: 7084 AN: 86254

European-Finnish (FIN) AF: 0.0854 AC: 4558 AN: 53394

Middle Eastern (MID) AF: 0.0826 AC: 476 AN: 5766

European-Non Finnish (NFE) AF: 0.0749 AC: 83287 AN: 1111960

Other (OTH) AF: 0.0998 AC: 6025 AN: 60394

GnomAD4 genome AF: 0.180 AC: 27367 AN: 152022 Hom.: 4248 Cov.: 32 AF XY: 0.179 AC XY: 13326 AN XY: 74336

African (AFR) AF: 0.425 AC: 17599 AN: 41426

American (AMR) AF: 0.154 AC: 2354 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0444 AC: 154 AN: 3468

East Asian (EAS) AF: 0.105 AC: 543 AN: 5160

South Asian (SAS) AF: 0.0802 AC: 386 AN: 4814

European-Finnish (FIN) AF: 0.0816 AC: 864 AN: 10582

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0738 AC: 5013 AN: 67970

Other (OTH) AF: 0.158 AC: 334 AN: 2110

Alfa AF: 0.113 Hom.: 1990

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
PhyloP100		-3.6
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: rs1042728; hg19: chr19-14581063;