chr16-2597733-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_002613.5(PDPK1):​c.1637G>A​(p.Arg546Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000992 in 1,613,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

PDPK1
NM_002613.5 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.33
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 Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.085276395).
BS2
High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PDPK1NM_002613.5 linkuse as main transcriptc.1637G>A p.Arg546Gln missense_variant 14/14 ENST00000342085.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PDPK1ENST00000342085.9 linkuse as main transcriptc.1637G>A p.Arg546Gln missense_variant 14/141 NM_002613.5 P1O15530-1
PDPK1ENST00000268673.11 linkuse as main transcriptc.1256G>A p.Arg419Gln missense_variant 11/111 O15530-4
PDPK1ENST00000441549.7 linkuse as main transcriptc.*61G>A 3_prime_UTR_variant 12/121 O15530-5
PDPK1ENST00000389224.7 linkuse as main transcriptc.1556G>A p.Arg519Gln missense_variant 14/142

Frequencies

GnomAD3 genomes
AF:
0.0000328
AC:
5
AN:
152228
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000121
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:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250618
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135602
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000753
AC:
11
AN:
1460878
Hom.:
0
Cov.:
31
AF XY:
0.00000550
AC XY:
4
AN XY:
726748
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000720
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152346
Hom.:
0
Cov.:
33
AF XY:
0.0000268
AC XY:
2
AN XY:
74500
show subpopulations
Gnomad4 AFR
AF:
0.000120
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:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000132
Hom.:
0
Bravo
AF:
0.0000680
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0

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 submitterclinical testingAmbry GeneticsJul 27, 2022The c.1637G>A (p.R546Q) alteration is located in exon 14 (coding exon 14) of the PDPK1 gene. This alteration results from a G to A substitution at nucleotide position 1637, causing the arginine (R) at amino acid position 546 to be replaced by a glutamine (Q). 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
0.090
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.35
T;.;T
Eigen
Benign
-0.14
Eigen_PC
Benign
0.020
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.86
D;D;D
M_CAP
Benign
0.0095
T
MetaRNN
Benign
0.085
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.55
N;.;.
MutationTaster
Benign
0.82
D;D;D;D;N
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-0.16
N;N;N
REVEL
Benign
0.039
Sift
Benign
0.29
T;T;T
Sift4G
Benign
0.29
T;T;T
Polyphen
0.93
P;B;.
Vest4
0.15
MVP
0.51
MPC
1.4
ClinPred
0.19
T
GERP RS
4.1
Varity_R
0.22
gMVP
0.44

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: rs148008907; hg19: chr16-2647734; API