chr16-2557854-G-A

Position:

• chr16-2557854-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002613.5(PDPK1):​c.176G>A​(p.Arg59Gln) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 24)
  • Exomes 𝑓: 0.000012 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PDPK1 NM_002613.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.78

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.20837528).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDPK1	NM_002613.5	c.176G>A	p.Arg59Gln	missense_variant	2/14	ENST00000342085.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDPK1	ENST00000342085.9	c.176G>A	p.Arg59Gln	missense_variant	2/14	1	NM_002613.5	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1 AN: 149968 Hom.: 0 Cov.: 24 FAILED QC

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: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000116 AC: 16 AN: 1380190 Hom.: 0 Cov.: 25 AF XY: 0.0000174 AC XY: 12 AN XY: 690324

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000226

Gnomad4 ASJ exome AF: 0.0000389

Gnomad4 EAS exome AF: 0.0000258

Gnomad4 SAS exome AF: 0.0000119

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000106

Gnomad4 OTH exome AF: 0.0000174

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000667 AC: 1 AN: 149968 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 73066

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: 0.0000148

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ExAC AF: 0.00000875 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.42	T;.;.;T;.
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.52
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.71	T;T;T;T;T
M_CAP	Uncertain	0.086	D
MetaRNN	Benign	0.21	T;T;T;T;T
MetaSVM	Benign	-0.78	T
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.91	N;N;N;N;N
REVEL	Benign	0.17
Sift	Benign	0.070	T;T;D;T;T
Sift4G	Benign	0.32	T;T;T;T;T
Polyphen		0.84	P;.;D;.;.
Vest4		0.17
MutPred		0.17		Loss of glycosylation at P60 (P = 0.1705);Loss of glycosylation at P60 (P = 0.1705);Loss of glycosylation at P60 (P = 0.1705);.;.;
MVP		0.73
MPC		2.1
ClinPred		0.11	T
GERP RS		3.3
Varity_R		0.035
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

Other links and lift over

dbSNP: rs779166111; hg19: chr16-2607855;