rs760608934

Variant names:

• chr19-14441204-C-A
• rs760608934
• NM_002741.5:c.83C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-14441204-C-A
• chr19-14441204-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002741.5(PKN1):​c.83C>A​(p.Ala28Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000415 in 1,444,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict 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. A28V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: PKN1 NM_002741.5 missense
• Clinical Significance: Not reported in ClinVar
• 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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054931313).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKN1	NM_002741.5	c.83C>A	p.Ala28Asp	missense_variant	Exon 2 of 22	ENST00000242783.11	NP_002732.3
PKN1	NM_213560.3	c.101C>A	p.Ala34Asp	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.83C>A	p.Ala28Asp	missense_variant	Exon 2 of 22	1	NM_002741.5	ENSP00000242783.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000415 AC: 6 AN: 1444056 Hom.: 0 Cov.: 32 AF XY: 0.00000418 AC XY: 3 AN XY: 717956

African (AFR) AF: 0.00 AC: 0 AN: 32250

American (AMR) AF: 0.00 AC: 0 AN: 41478

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25416

East Asian (EAS) AF: 0.00 AC: 0 AN: 38754

South Asian (SAS) AF: 0.00 AC: 0 AN: 84086

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51128

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 0.00000543 AC: 6 AN: 1105628

Other (OTH) AF: 0.00 AC: 0 AN: 59616

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	20
DANN	Benign	0.80
DEOGEN2	Benign	0.062	T;.;T;.
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.78	T;T;T;T
M_CAP	Uncertain	0.085	D
MetaRNN	Benign	0.055	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.6	N;.;.;.
PhyloP100		4.6
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	4.3	N;.;.;N
REVEL	Benign	0.066
Sift	Benign	1.0	T;.;.;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0010	B;.;.;B
Vest4		0.26
MutPred		0.22		Gain of loop (P = 0.024);.;.;.;
MVP		0.14
MPC		0.50
ClinPred		0.12	T
GERP RS		4.1
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7
Varity_R		0.29
gMVP		0.25
Mutation Taster		=77/23	polymorphism

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: rs760608934; hg19: chr19-14552016;