Genetic Variant PKN1:c.21+1188C>T (chr19-14434730-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.307

Publications

6 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002741.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKN1	NM_002741.5	MANE Select	c.21+1188C>T		intron	N/A	NP_002732.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PKN1	ENST00000242783.11	TSL:1 MANE Select	c.21+1188C>T	intron	N/A	ENSP00000242783.7
PKN1	ENST00000590097.5	TSL:3	c.57+76C>T	intron	N/A	ENSP00000466367.1
PKN1	ENST00000586557.5	TSL:5	c.57+76C>T	intron	N/A	ENSP00000465842.1

Frequencies

GnomAD3 genomes

AF:

0.137

AC:

20767

AN:

152134

Hom.:

2037

Cov.:

show subpopulations

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:

AN:

142

Hom.:

AF XY:

0.0556

AC XY:

AN XY:

108

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.0625

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0741

AC:

AN:

108

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.137

AC:

20804

AN:

152252

Hom.:

2051

Cov.:

AF XY:

0.142

AC XY:

10557

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.103

AC:

4261

AN:

41560

American (AMR)

AF:

0.160

AC:

2446

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.131

AC:

456

AN:

3468

East Asian (EAS)

AF:

0.530

AC:

2731

AN:

5148

South Asian (SAS)

AF:

0.338

AC:

1632

AN:

4834

European-Finnish (FIN)

AF:

0.105

AC:

1110

AN:

10618

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.113

AC:

7702

AN:

68012

Other (OTH)

AF:

0.157

AC:

333

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

893

1785

2678

3570

4463

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

232

464

696

928

1160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.124

Hom.:

3969

Bravo

AF:

0.138

Asia WGS

AF:

0.443

AC:

1539

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

(source)

DANN

Benign

0.74

PhyloP100

0.31

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over