19-14441204-C-T
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The ENST00000242783.11(PKN1):c.83C>T(p.Ala28Val) variant causes a missense change. The variant allele was found at a frequency of 0.000089 in 1,596,214 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000088 ( 0 hom. )
Consequence
PKN1
ENST00000242783.11 missense
ENST00000242783.11 missense
Scores
1
6
12
Clinical Significance
Conservation
PhyloP100: 4.64
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 -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.026023954).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PKN1 | NM_002741.5 | c.83C>T | p.Ala28Val | missense_variant | 2/22 | ENST00000242783.11 | NP_002732.3 | |
PKN1 | NM_213560.3 | c.101C>T | p.Ala34Val | missense_variant | 2/22 | NP_998725.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PKN1 | ENST00000242783.11 | c.83C>T | p.Ala28Val | missense_variant | 2/22 | 1 | NM_002741.5 | ENSP00000242783 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000986 AC: 15AN: 152158Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000160 AC: 34AN: 212558Hom.: 0 AF XY: 0.000161 AC XY: 19AN XY: 118130
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GnomAD4 exome AF: 0.0000879 AC: 127AN: 1444056Hom.: 0 Cov.: 32 AF XY: 0.0000864 AC XY: 62AN XY: 717956
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GnomAD4 genome AF: 0.0000986 AC: 15AN: 152158Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74326
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 10, 2022 | The c.101C>T (p.A34V) alteration is located in exon 2 (coding exon 2) of the PKN1 gene. This alteration results from a C to T substitution at nucleotide position 101, causing the alanine (A) at amino acid position 34 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;.;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
T
PROVEAN
Benign
N;.;.;N
REVEL
Benign
Sift
Uncertain
D;.;.;D
Sift4G
Uncertain
D;D;D;T
Polyphen
P;.;.;D
Vest4
MutPred
Gain of loop (P = 0.024);.;.;.;
MVP
MPC
0.85
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at