9-128707288-C-A

Variant summary

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

The NM_013355.5(PKN3):c.718C>A(p.Leu240Met) variant causes a missense 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PKN3 NM_013355.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.74

Genes affected

PKN3 (HGNC:17999): (protein kinase N3) Predicted to enable protein serine/threonine kinase activity. Involved in epithelial cell migration. Predicted to be located in Golgi apparatus and cytosol. [provided by Alliance of Genome Resources, Apr 2022]

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=0.14407653).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKN3	NM_013355.5	c.718C>A	p.Leu240Met	missense_variant	6/22	ENST00000291906.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKN3	ENST00000291906.5	c.718C>A	p.Leu240Met	missense_variant	6/22	1	NM_013355.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 13, 2023

The c.718C>A (p.L240M) alteration is located in exon 6 (coding exon 6) of the PKN3 gene. This alteration results from a C to A substitution at nucleotide position 718, causing the leucine (L) at amino acid position 240 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
Cadd	Benign	22
Dann	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Benign	0.10
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.034
Sift	Benign	0.060	T
Sift4G	Benign	0.098	T
Polyphen		0.44	B
Vest4		0.30
MutPred		0.28		Gain of MoRF binding (P = 0.3961);
MVP		0.17
MPC		0.57
ClinPred		0.47	T
GERP RS		2.2
Varity_R		0.21
gMVP		0.29

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: chr9-131469567;