Variant 19-14443582-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The ENST00000242783.11(PKN1):c.435G>A(p.Ala145=) 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
ENST00000242783.11 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -7.11

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 -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 id 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKN1	NM_002741.5 linkuse as main transcript	c.435G>A	p.Ala145=	synonymous_variant	3/22	ENST00000242783.11	NP_002732.3
PKN1	NM_213560.3 linkuse as main transcript	c.453G>A	p.Ala151=	synonymous_variant	3/22		NP_998725.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKN1	ENST00000242783.11 linkuse as main transcript	c.435G>A	p.Ala145=	synonymous_variant	3/22	1	NM_002741.5	ENSP00000242783	P4	Q16512-1

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

GnomAD3 exomes

AF:

0.00522

AC:

1297

AN:

248672

Hom.:

AF XY:

0.00515

AC XY:

693

AN XY:

134634

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 SAS exome

AF:

0.0000656

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

Gnomad4 AFR exome

AF:

0.00117

Gnomad4 AMR exome

AF:

0.000987

Gnomad4 ASJ exome

AF:

0.000575

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000929

Gnomad4 FIN exome

AF:

0.0105

Gnomad4 NFE exome

AF:

0.00813

Gnomad4 OTH exome

AF:

0.00487

GnomAD4 genome

AF:

0.00483

AC:

736

AN:

152286

Hom.:

Cov.:

AF XY:

0.00451

AC XY:

336

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00147

Gnomad4 AMR

AF:

0.00163

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00659

Gnomad4 NFE

AF:

0.00831

Gnomad4 OTH

AF:

0.00473

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

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

1.8

DANN

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over