Variant 16-2597689-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_002613.5(PDPK1):c.1593C>T(p.Asn531=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000516 in 1,613,712 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00056 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00051 ( 1 hom. )

Consequence

PDPK1
NM_002613.5 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.228

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 16-2597689-C-T is Benign according to our data. Variant chr16-2597689-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3033227.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.228 with no splicing effect.

BS2

High AC in GnomAd4 at 86 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDPK1	NM_002613.5 linkuse as main transcript	c.1593C>T	p.Asn531=	synonymous_variant	14/14	ENST00000342085.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDPK1	ENST00000342085.9 linkuse as main transcript	c.1593C>T	p.Asn531=	synonymous_variant	14/14	1	NM_002613.5	P1	O15530-1
PDPK1	ENST00000268673.11 linkuse as main transcript	c.1212C>T	p.Asn404=	synonymous_variant	11/11	1			O15530-4
PDPK1	ENST00000441549.7 linkuse as main transcript	c.*17C>T		3_prime_UTR_variant	12/12	1			O15530-5
PDPK1	ENST00000389224.7 linkuse as main transcript	c.1512C>T	p.Asn504=	synonymous_variant	14/14	2

Frequencies

GnomAD3 genomes

AF:

0.000565

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000897

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000636

AC:

159

AN:

250184

Hom.:

AF XY:

0.000613

AC XY:

AN XY:

135330

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000894

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00236

Gnomad NFE exome

AF:

0.000836

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000510

AC:

746

AN:

1461378

Hom.:

Cov.:

AF XY:

0.000536

AC XY:

390

AN XY:

726986

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000804

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00245

Gnomad4 NFE exome

AF:

0.000507

Gnomad4 OTH exome

AF:

0.000447

GnomAD4 genome

AF:

0.000565

AC:

AN:

152334

Hom.:

Cov.:

AF XY:

0.000604

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00188

Gnomad4 NFE

AF:

0.000897

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000671

Hom.:

Bravo

AF:

0.000389

EpiCase

AF:

0.000491

EpiControl

AF:

0.000356

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PDPK1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 18, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

2.9

DANN

Benign

0.91

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

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