Variant chr16-2557829-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002613.5(PDPK1):c.151A>G(p.Met51Val) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 24)

Exomes 𝑓: 0.000022 ( 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: 7.10

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.24617645).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDPK1	NM_002613.5 linkuse as main transcript	c.151A>G	p.Met51Val	missense_variant	2/14	ENST00000342085.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDPK1	ENST00000342085.9 linkuse as main transcript	c.151A>G	p.Met51Val	missense_variant	2/14	1	NM_002613.5	P1	O15530-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

147798

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000527

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000269

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000223

AC:

AN:

1303058

Hom.:

Cov.:

AF XY:

0.0000214

AC XY:

AN XY:

654494

show subpopulations

Gnomad4 AFR exome

AF:

0.000799

Gnomad4 AMR exome

AF:

0.0000469

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000123

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000103

Gnomad4 OTH exome

AF:

0.0000183

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000169

AC:

AN:

147904

Hom.:

Cov.:

AF XY:

0.000167

AC XY:

AN XY:

71912

show subpopulations

Gnomad4 AFR

AF:

0.000526

Gnomad4 AMR

AF:

0.000269

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000547

AC:

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

Jul 14, 2021

The c.151A>G (p.M51V) alteration is located in exon 2 (coding exon 2) of the PDPK1 gene. This alteration results from a A to G substitution at nucleotide position 151, causing the methionine (M) at amino acid position 51 to be replaced by a valine (V). 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

0.060

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.36

T;.;.;T;.

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.11

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.73

T;T;T;T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.25

T;T;T;T;T

MetaSVM

Benign

-0.88

MutationTaster

Benign

1.0

D;D;D;D;N

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.39

N;N;N;N;N

REVEL

Benign

0.24

Sift

Benign

0.36

T;T;D;T;T

Sift4G

Benign

0.34

T;T;T;T;T

Polyphen

0.025

B;.;B;.;.

Vest4

0.48

MutPred

0.17

Gain of glycosylation at T54 (P = 0.1706);Gain of glycosylation at T54 (P = 0.1706);Gain of glycosylation at T54 (P = 0.1706);.;.;

MVP

0.74

MPC

1.9

ClinPred

0.061

GERP RS

4.4

Varity_R

0.31

gMVP

0.42

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over