rs10866

Positions:

• chr16-2597875-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_002613.5(PDPK1):​c.*108C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0489 in 678,864 control chromosomes in the GnomAD database, including 1,058 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.041 (173 hom., cov: 33)
  • Exomes 𝑓: 0.051 (885 hom.)
• Consequence: PDPK1 NM_002613.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDPK1	NM_002613.5	c.*108C>T		3_prime_UTR_variant	14/14	ENST00000342085.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDPK1	ENST00000342085.9	c.*108C>T		3_prime_UTR_variant	14/14	1	NM_002613.5	P1
	ENST00000562166.1			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0410 AC: 6238 AN: 152210 Hom.: 173 Cov.: 33

Gnomad AFR AF: 0.00881

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0334

Gnomad ASJ AF: 0.0709

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0496

Gnomad FIN AF: 0.0721

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0582

Gnomad OTH AF: 0.0349

GnomAD4 exome AF: 0.0512 AC: 26965 AN: 526536 Hom.: 885 Cov.: 6 AF XY: 0.0522 AC XY: 14620 AN XY: 280322

Gnomad4 AFR exome AF: 0.00793

Gnomad4 AMR exome AF: 0.0255

Gnomad4 ASJ exome AF: 0.0621

Gnomad4 EAS exome AF: 0.000124

Gnomad4 SAS exome AF: 0.0562

Gnomad4 FIN exome AF: 0.0773

Gnomad4 NFE exome AF: 0.0554

Gnomad4 OTH exome AF: 0.0487

GnomAD4 genome AF: 0.0409 AC: 6237 AN: 152328 Hom.: 173 Cov.: 33 AF XY: 0.0420 AC XY: 3127 AN XY: 74490

Gnomad4 AFR AF: 0.00878

Gnomad4 AMR AF: 0.0333

Gnomad4 ASJ AF: 0.0709

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.0501

Gnomad4 FIN AF: 0.0721

Gnomad4 NFE AF: 0.0582

Gnomad4 OTH AF: 0.0336

Alfa AF: 0.0492 Hom.: 88

Bravo AF: 0.0345

Asia WGS AF: 0.0190 AC: 67 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	11
DANN	Benign	0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs10866; hg19: chr16-2647876;