Genetic Variant PKN1:p.Ala145Ala (chr19-14443582-G-A) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_002741.5(PKN1):c.435G>A(p.Ala145Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00665 in 1,613,260 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0048 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0068 ( 29 hom. )

Consequence

PKN1
NM_002741.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -7.11

Publications

2 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 19-14443582-G-A is Benign according to our data. Variant chr19-14443582-G-A is described in ClinVar as Benign. ClinVar VariationId is 774732.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-7.11 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKN1	NM_002741.5	MANE Select	c.435G>A	p.Ala145Ala	synonymous	Exon 3 of 22	NP_002732.3
	PKN1	NM_213560.3		c.453G>A	p.Ala151Ala	synonymous	Exon 3 of 22	NP_998725.1	Q16512-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PKN1	ENST00000242783.11	TSL:1 MANE Select	c.435G>A	p.Ala145Ala	synonymous	Exon 3 of 22	ENSP00000242783.7	Q16512-1
PKN1	ENST00000900936.1		c.435G>A	p.Ala145Ala	synonymous	Exon 3 of 23	ENSP00000570995.1
PKN1	ENST00000342216.8	TSL:2	c.453G>A	p.Ala151Ala	synonymous	Exon 3 of 22	ENSP00000343325.4	Q16512-2

Frequencies

GnomAD3 genomes

AF:

0.00484

AC:

736

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00147

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00659

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00831

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.00522

AC:

1297

AN:

248672

AF XY:

0.00515

show subpopulations

Gnomad AFR exome

AF:

0.00101

Gnomad AMR exome

AF:

0.00126

Gnomad ASJ exome

AF:

0.000602

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00889

Gnomad NFE exome

AF:

0.00898

Gnomad OTH exome

AF:

0.00466

GnomAD4 exome

AF:

0.00684

AC:

9998

AN:

1460974

Hom.:

Cov.:

AF XY:

0.00659

AC XY:

4791

AN XY:

726756

show subpopulations

African (AFR)

AF:

0.00117

AC:

AN:

33460

American (AMR)

AF:

0.000987

AC:

AN:

44598

Ashkenazi Jewish (ASJ)

AF:

0.000575

AC:

AN:

26070

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39686

South Asian (SAS)

AF:

0.0000929

AC:

AN:

86132

European-Finnish (FIN)

AF:

0.0105

AC:

562

AN:

53396

Middle Eastern (MID)

AF:

0.000348

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00813

AC:

9033

AN:

1111536

Other (OTH)

AF:

0.00487

AC:

294

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

518

1037

1555

2074

2592

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

314

628

942

1256

1570

<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:

0.00483

AC:

736

AN:

152286

Hom.:

Cov.:

AF XY:

0.00451

AC XY:

336

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.00147

AC:

AN:

41550

American (AMR)

AF:

0.00163

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00659

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00831

AC:

565

AN:

67994

Other (OTH)

AF:

0.00473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

124

165

206

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00633

Hom.:

Bravo

AF:

0.00422

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00769

EpiControl

AF:

0.00691

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

1.8

(source)

DANN

Benign

0.81

PhyloP100

-7.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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