Variant chr16-2597216-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_002613.5(PDPK1):c.1495C>A(p.Pro499Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,444,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PDPK1
NM_002613.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.68

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.748

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDPK1	NM_002613.5 linkuse as main transcript	c.1495C>A	p.Pro499Thr	missense_variant	13/14	ENST00000342085.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDPK1	ENST00000342085.9 linkuse as main transcript	c.1495C>A	p.Pro499Thr	missense_variant	13/14	1	NM_002613.5	P1	O15530-1
PDPK1	ENST00000268673.11 linkuse as main transcript	c.1114C>A	p.Pro372Thr	missense_variant	10/11	1			O15530-4
PDPK1	ENST00000441549.7 linkuse as main transcript	c.1344-435C>A		intron_variant		1			O15530-5
PDPK1	ENST00000389224.7 linkuse as main transcript	c.1414C>A	p.Pro472Thr	missense_variant	13/14	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.92e-7

AC:

AN:

1444614

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

714818

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

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.:

Bravo

AF:

0.00000378

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 09, 2021

The c.1495C>A (p.P499T) alteration is located in exon 13 (coding exon 13) of the PDPK1 gene. This alteration results from a C to A substitution at nucleotide position 1495, causing the proline (P) at amino acid position 499 to be replaced by a threonine (T). 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

Pathogenic

0.99

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.030

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.88

D;.;T

Eigen

Pathogenic

0.88

Eigen_PC

Pathogenic

0.83

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Benign

0.046

MetaRNN

Pathogenic

0.75

D;D;D

MetaSVM

Benign

-0.68

MutationAssessor

Pathogenic

3.3

M;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Pathogenic

-6.6

D;D;D

REVEL

Uncertain

0.48

Sift

Uncertain

0.0040

D;D;D

Sift4G

Uncertain

0.0070

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.78

MutPred

0.36

Gain of helix (P = 0.0225);.;.;

MVP

0.60

MPC

2.3

ClinPred

0.99

GERP RS

5.0

Varity_R

0.85

gMVP

0.60

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