chr16-2597733-G-A
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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
NM_002613.5 missense
Scores
3
16
Clinical Significance
Conservation
PhyloP100: 4.33
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]
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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 |
---|---|---|---|---|---|---|---|
PDPK1 | NM_002613.5 | c.1637G>A | p.Arg546Gln | missense_variant | 14/14 | ENST00000342085.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDPK1 | ENST00000342085.9 | c.1637G>A | p.Arg546Gln | missense_variant | 14/14 | 1 | NM_002613.5 | P1 | |
PDPK1 | ENST00000268673.11 | c.1256G>A | p.Arg419Gln | missense_variant | 11/11 | 1 | |||
PDPK1 | ENST00000441549.7 | c.*61G>A | 3_prime_UTR_variant | 12/12 | 1 | ||||
PDPK1 | ENST00000389224.7 | c.1556G>A | p.Arg519Gln | missense_variant | 14/14 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152228Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250618Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135602
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GnomAD4 exome AF: 0.00000753 AC: 11AN: 1460878Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 726748
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GnomAD4 genome AF: 0.0000328 AC: 5AN: 152346Hom.: 0 Cov.: 33 AF XY: 0.0000268 AC XY: 2AN XY: 74500
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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 27, 2022 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;.
MutationTaster
Benign
D;D;D;D;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
P;B;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at