19-14443582-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_002741.5(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 NM_002741.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -7.11

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 -9 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_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-7.11 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKN1	NM_002741.5	c.435G>A	p.Ala145=	synonymous_variant	3/22	ENST00000242783.11
PKN1	NM_213560.3	c.453G>A	p.Ala151=	synonymous_variant	3/22

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00484 AC: 736 AN: 152168 Hom.: 3 Cov.: 33

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.: 4 AF XY: 0.00515 AC XY: 693 AN XY: 134634

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.: 29 Cov.: 31 AF XY: 0.00659 AC XY: 4791 AN XY: 726756

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.: 3 Cov.: 33 AF XY: 0.00451 AC XY: 336 AN XY: 74448

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.: 1

Bravo AF: 0.00422

Asia WGS AF: 0.00115 AC: 5 AN: 3478

EpiCase AF: 0.00769

EpiControl AF: 0.00691

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 06, 2018

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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

Other links and lift over

dbSNP: rs55814382; hg19: chr19-14554394;