chr16-2597749-G-A

Variant summary

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

The NM_002613.5(PDPK1):​c.1653G>A​(p.Pro551=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,611,788 control chromosomes in the GnomAD database, including 1 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 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000016 ( 1 hom. )

Consequence

PDPK1
NM_002613.5 synonymous

Scores

2

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.54
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]

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=-0.8).
BP6
Variant 16-2597749-G-A is Benign according to our data. Variant chr16-2597749-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3046933.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=-1.54 with no splicing effect.
BS2
High AC in GnomAdExome4 at 24 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PDPK1NM_002613.5 linkuse as main transcriptc.1653G>A p.Pro551= synonymous_variant 14/14 ENST00000342085.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PDPK1ENST00000342085.9 linkuse as main transcriptc.1653G>A p.Pro551= synonymous_variant 14/141 NM_002613.5 P1O15530-1
PDPK1ENST00000268673.11 linkuse as main transcriptc.1272G>A p.Pro424= synonymous_variant 11/111 O15530-4
PDPK1ENST00000441549.7 linkuse as main transcriptc.*77G>A 3_prime_UTR_variant 12/121 O15530-5
PDPK1ENST00000389224.7 linkuse as main transcriptc.1572G>A p.Pro524= synonymous_variant 14/142

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152228
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000799
AC:
2
AN:
250216
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135486
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000177
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000164
AC:
24
AN:
1459560
Hom.:
1
Cov.:
30
AF XY:
0.0000165
AC XY:
12
AN XY:
726138
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000171
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152228
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74370
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 providedclinical testingPreventionGenetics, part of Exact SciencesMar 13, 2019This 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
-0.80
CADD
Benign
0.61
DANN
Benign
0.90
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.

Other links and lift over

dbSNP: rs747477279; hg19: chr16-2647750; COSMIC: COSV51912564; COSMIC: COSV51912564; API