Variant rs45569335 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005030.6(PLK1):c.1388T>A(p.Leu463His) variant causes a missense change. The variant allele was found at a frequency of 0.00963 in 1,612,956 control chromosomes in the GnomAD database, including 99 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0065 ( 4 hom., cov: 32)

Exomes 𝑓: 0.010 ( 95 hom. )

Consequence

PLK1
NM_005030.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.59

Variant links:

Genes affected

PLK1 (HGNC:9077): (polo like kinase 1) The Ser/Thr protein kinase encoded by this gene belongs to the CDC5/Polo subfamily. It is highly expressed during mitosis and elevated levels are found in many different types of cancer. Depletion of this protein in cancer cells dramatically inhibited cell proliferation and induced apoptosis; hence, it is a target for cancer therapy. [provided by RefSeq, Sep 2015]

PLK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008825004).

BS2

High AC in GnomAd4 at 987 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLK1	NM_005030.6 linkuse as main transcript	c.1388T>A	p.Leu463His	missense_variant	8/10	ENST00000300093.9	NP_005021.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
PLK1	ENST00000300093.9 linkuse as main transcript	c.1388T>A	p.Leu463His	missense_variant	8/10	1	NM_005030.6	ENSP00000300093	P1
PLK1	ENST00000562272.5 linkuse as main transcript	n.3408T>A		non_coding_transcript_exon_variant	7/9	2
PLK1	ENST00000564794.1 linkuse as main transcript	n.188T>A		non_coding_transcript_exon_variant	2/4	5

Frequencies

GnomAD3 genomes

AF:

0.00649

AC:

987

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00232

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00641

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0112

Gnomad OTH

AF:

0.00622

GnomAD3 exomes

AF:

0.00609

AC:

1531

AN:

251382

Hom.:

AF XY:

0.00599

AC XY:

814

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.00215

Gnomad AMR exome

AF:

0.00425

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.00203

Gnomad NFE exome

AF:

0.0111

Gnomad OTH exome

AF:

0.00554

GnomAD4 exome

AF:

0.00995

AC:

14540

AN:

1460686

Hom.:

Cov.:

AF XY:

0.00959

AC XY:

6968

AN XY:

726390

show subpopulations

Gnomad4 AFR exome

AF:

0.00158

Gnomad4 AMR exome

AF:

0.00465

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000429

Gnomad4 FIN exome

AF:

0.00253

Gnomad4 NFE exome

AF:

0.0123

Gnomad4 OTH exome

AF:

0.00663

GnomAD4 genome

AF:

0.00648

AC:

987

AN:

152270

Hom.:

Cov.:

AF XY:

0.00600

AC XY:

447

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00231

Gnomad4 AMR

AF:

0.00641

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00160

Gnomad4 NFE

AF:

0.0112

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00919

Hom.:

Bravo

AF:

0.00693

TwinsUK

AF:

0.0116

AC:

ALSPAC

AF:

0.0125

AC:

ESP6500AA

AF:

0.00341

AC:

ESP6500EA

AF:

0.0100

AC:

ExAC

AF:

0.00630

AC:

765

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00867

EpiControl

AF:

0.00806

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Uncertain

-0.070

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.044

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.031

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.78

MetaRNN

Benign

0.0088

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.050

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.60

PROVEAN

Benign

1.5

REVEL

Benign

0.24

Sift

Benign

0.21

Sift4G

Benign

0.21

Polyphen

0.0010

Vest4

0.53

MVP

0.82

MPC

1.0

ClinPred

0.018

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.62

gMVP

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over