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GeneBe

19-14450400-T-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_002741.5(PKN1):c.693T>C(p.Gly231=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000418 in 1,603,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

PKN1
NM_002741.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.82
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.66).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 19-14450400-T-C is Benign according to our data. Variant chr19-14450400-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 728835.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.82 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PKN1NM_002741.5 linkuse as main transcriptc.693T>C p.Gly231= synonymous_variant 5/22 ENST00000242783.11
PKN1NM_213560.3 linkuse as main transcriptc.711T>C p.Gly237= synonymous_variant 5/22

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PKN1ENST00000242783.11 linkuse as main transcriptc.693T>C p.Gly231= synonymous_variant 5/221 NM_002741.5 P4Q16512-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000151
AC:
23
AN:
152110
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000507
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000711
AC:
16
AN:
225142
Hom.:
0
AF XY:
0.0000408
AC XY:
5
AN XY:
122676
show subpopulations
Gnomad AFR exome
AF:
0.000609
Gnomad AMR exome
AF:
0.000156
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000197
Gnomad OTH exome
AF:
0.000181
GnomAD4 exome
AF:
0.0000303
AC:
44
AN:
1450888
Hom.:
0
Cov.:
31
AF XY:
0.0000319
AC XY:
23
AN XY:
720864
show subpopulations
Gnomad4 AFR exome
AF:
0.000540
Gnomad4 AMR exome
AF:
0.000140
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000238
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000108
Gnomad4 OTH exome
AF:
0.0000835
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000151
AC:
23
AN:
152228
Hom.:
0
Cov.:
32
AF XY:
0.000161
AC XY:
12
AN XY:
74418
show subpopulations
Gnomad4 AFR
AF:
0.000506
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000155
Hom.:
0
Bravo
AF:
0.000162
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeMay 08, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.66
Cadd
Benign
6.2
Dann
Benign
0.76

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.

Other links and lift over

dbSNP: rs200219286; hg19: chr19-14561212; API