rs12463361

Positions:

• chr19-14434730-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002741.5(PKN1):​c.21+1188C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,394 control chromosomes in the GnomAD database, including 2,051 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 0.14 (2051 hom., cov: 33)
  • Exomes 𝑓: 0.085 (0 hom.)
• Consequence: PKN1 NM_002741.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.307

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKN1	NM_002741.5	c.21+1188C>T		intron_variant		ENST00000242783.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKN1	ENST00000242783.11	c.21+1188C>T		intron_variant		1	NM_002741.5	P4

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20767 AN: 152134 Hom.: 2037 Cov.: 33

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.149

GnomAD4 exome AF: 0.0845 AC: 12 AN: 142 Hom.: 0 AF XY: 0.0556 AC XY: 6 AN XY: 108

Gnomad4 AFR exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0625

Gnomad4 NFE exome AF: 0.0741

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.137 AC: 20804 AN: 152252 Hom.: 2051 Cov.: 33 AF XY: 0.142 AC XY: 10557 AN XY: 74422

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.530

Gnomad4 SAS AF: 0.338

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.157

Alfa AF: 0.123 Hom.: 1608

Bravo AF: 0.138

Asia WGS AF: 0.443 AC: 1539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	14
DANN	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs12463361; hg19: chr19-14545542;