chr19-14441368-C-A

Variant names:

• chr19-14441368-C-A
• NM_002741.5:c.247C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002741.5(PKN1):​c.247C>A​(p.Arg83Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000737 in 1,357,486 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R83C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: PKN1 NM_002741.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.358

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26243937).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKN1	NM_002741.5	c.247C>A	p.Arg83Ser	missense_variant	Exon 2 of 22	ENST00000242783.11	NP_002732.3
PKN1	NM_213560.3	c.265C>A	p.Arg89Ser	missense_variant	Exon 2 of 22		NP_998725.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKN1	ENST00000242783.11	c.247C>A	p.Arg83Ser	missense_variant	Exon 2 of 22	1	NM_002741.5	ENSP00000242783.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.37e-7 AC: 1 AN: 1357486 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 668510

Gnomad4 AFR exome AF: 0.0000354

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T;.;T;.
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.048	N
LIST_S2	Uncertain	0.97	D;D;D;D
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.26	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.9	L;.;.;.
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.6	D;.;.;D
REVEL	Benign	0.093
Sift	Uncertain	0.0040	D;.;.;D
Sift4G	Uncertain	0.0070	D;D;D;D
Polyphen		0.96	D;.;.;P
Vest4		0.39
MutPred		0.64		Gain of phosphorylation at R83 (P = 0.0417);.;.;.;
MVP		0.35
MPC		1.0
ClinPred		0.82	D
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.73
gMVP		0.33

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-14552180;