chr19-14443582-G-C

Variant names:

• chr19-14443582-G-C
• NM_002741.5:c.435G>C
• PKN1 p.Ala145Ala

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_002741.5(PKN1):​c.435G>C​(p.Ala145Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A145A) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PKN1 NM_002741.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -7.11
• Publications: 0 publications found

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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP7: Synonymous conserved (PhyloP=-7.11 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002741.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKN1	NM_002741.5	MANE Select	c.435G>C	p.Ala145Ala	synonymous	Exon 3 of 22	NP_002732.3
	PKN1	NM_213560.3		c.453G>C	p.Ala151Ala	synonymous	Exon 3 of 22	NP_998725.1	Q16512-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKN1	ENST00000242783.11	TSL:1 MANE Select	c.435G>C	p.Ala145Ala	synonymous	Exon 3 of 22	ENSP00000242783.7	Q16512-1
	PKN1	ENST00000900936.1		c.435G>C	p.Ala145Ala	synonymous	Exon 3 of 23	ENSP00000570995.1
	PKN1	ENST00000342216.8	TSL:2	c.453G>C	p.Ala151Ala	synonymous	Exon 3 of 22	ENSP00000343325.4	Q16512-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.19
DANN	Benign	0.74
PhyloP100		-7.1
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-14554394;