Variant 16-2538129-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002613.5(PDPK1):c.17G>A(p.Ser6Asn) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PDPK1
NM_002613.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.64

Variant links:

Genes affected

PDPK1 (HGNC:8816): (3-phosphoinositide dependent protein kinase 1) Enables 3-phosphoinositide-dependent protein kinase activity; phospholipase activator activity; and phospholipase binding activity. Involved in several processes, including cell surface receptor signaling pathway; regulation of protein kinase activity; and regulation of signal transduction. Acts upstream of or within intracellular signal transduction. Located in cell projection; cytosol; and plasma membrane. Implicated in prostate cancer. Biomarker of lung non-small cell carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

PDPK1 links:

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ACMG classification

Classification made for transcript

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=0.17985791).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDPK1	NM_002613.5 link	c.17G>A	p.Ser6Asn	missense_variant	1/14	ENST00000342085.9	NP_002604.1	O15530-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDPK1	ENST00000342085.9 link	c.17G>A	p.Ser6Asn	missense_variant	1/14	1	NM_002613.5	ENSP00000344220.4		O15530-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

917248

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

429042

Gnomad4 AFR exome

AF:

0.00

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.:

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

Aug 28, 2024

The c.17G>A (p.S6N) alteration is located in exon 1 (coding exon 1) of the PDPK1 gene. This alteration results from a G to A substitution at nucleotide position 17, causing the serine (S) at amino acid position 6 to be replaced by an asparagine (N). 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

0.21

BayesDel_addAF

Benign

-0.064

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.55

D;.;.

Eigen

Benign

-0.055

Eigen_PC

Benign

-0.0096

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.70

T;T;T

M_CAP

Pathogenic

0.31

MetaRNN

Benign

0.18

T;T;T

MetaSVM

Benign

-0.64

MutationAssessor

Benign

0.63

N;N;N

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.44

N;N;N

REVEL

Benign

0.056

Sift

Benign

0.034

D;D;D

Sift4G

Uncertain

0.017

D;D;D

Polyphen

0.63

P;.;B

Vest4

0.21

MutPred

0.24

Loss of disorder (P = 0.0773);Loss of disorder (P = 0.0773);Loss of disorder (P = 0.0773);

MVP

0.63

MPC

1.7

ClinPred

0.38

GERP RS

2.9

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

3.7

Varity_R

0.16

gMVP

0.45

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over