rs10866

Variant names:

• chr16-2597875-C-T
• rs10866
• NM_002613.5:c.*108C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

ENSG00000261093 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002613.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDPK1	NM_002613.5	MANE Select	c.*108C>T		3_prime_UTR	Exon 14 of 14	NP_002604.1	O15530-1
	PDPK1	NM_001261816.2		c.*203C>T		3_prime_UTR	Exon 12 of 12	NP_001248745.1	O15530-5
	PDPK1	NM_031268.6		c.*108C>T		3_prime_UTR	Exon 11 of 11	NP_112558.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDPK1	ENST00000342085.9	TSL:1 MANE Select	c.*108C>T		3_prime_UTR	Exon 14 of 14	ENSP00000344220.4	O15530-1
	PDPK1	ENST00000441549.7	TSL:1	c.*203C>T		3_prime_UTR	Exon 12 of 12	ENSP00000395357.3	O15530-5
	PDPK1	ENST00000268673.12	TSL:1	c.*108C>T		3_prime_UTR	Exon 11 of 11	ENSP00000268673.7	O15530-4

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

African (AFR) AF: 0.00793 AC: 110 AN: 13866

American (AMR) AF: 0.0255 AC: 553 AN: 21664

Ashkenazi Jewish (ASJ) AF: 0.0621 AC: 974 AN: 15682

East Asian (EAS) AF: 0.000124 AC: 4 AN: 32302

South Asian (SAS) AF: 0.0562 AC: 2941 AN: 52324

European-Finnish (FIN) AF: 0.0773 AC: 3353 AN: 43376

Middle Eastern (MID) AF: 0.0523 AC: 114 AN: 2180

European-Non Finnish (NFE) AF: 0.0554 AC: 17525 AN: 316582

Other (OTH) AF: 0.0487 AC: 1391 AN: 28560

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

African (AFR) AF: 0.00878 AC: 365 AN: 41564

American (AMR) AF: 0.0333 AC: 510 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0709 AC: 246 AN: 3470

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5180

South Asian (SAS) AF: 0.0501 AC: 242 AN: 4832

European-Finnish (FIN) AF: 0.0721 AC: 766 AN: 10620

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0582 AC: 3961 AN: 68032

Other (OTH) AF: 0.0336 AC: 71 AN: 2112

Alfa AF: 0.0493 Hom.: 201

Bravo AF: 0.0345

Asia WGS AF: 0.0190 AC: 67 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	11
DANN	Benign	0.82
PhyloP100		-0.15
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs10866; hg19: chr16-2647876;