dbSNP rs45569335: PLK1:p.Leu463His (chr16-23689355-T-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

Publications

14 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PLK1	NM_005030.6 link	c.1388T>A	p.Leu463His	missense_variant	Exon 8 of 10	ENST00000300093.9	NP_005021.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
PLK1	ENST00000300093.9 link	c.1388T>A	p.Leu463His	missense_variant	Exon 8 of 10	1	NM_005030.6	ENSP00000300093.4
PLK1	ENST00000562272.5 link	n.3408T>A		non_coding_transcript_exon_variant	Exon 7 of 9	2
PLK1	ENST00000564794.1 link	n.188T>A		non_coding_transcript_exon_variant	Exon 2 of 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

GnomAD2 exomes

AF:

0.00609

AC:

1531

AN:

251382

AF XY:

0.00599

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 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

African (AFR)

AF:

0.00158

AC:

AN:

33468

American (AMR)

AF:

0.00465

AC:

208

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.0000765

AC:

AN:

26130

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39634

South Asian (SAS)

AF:

0.000429

AC:

AN:

86230

European-Finnish (FIN)

AF:

0.00253

AC:

135

AN:

53412

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0123

AC:

13702

AN:

1110992

Other (OTH)

AF:

0.00663

AC:

400

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

729

1459

2188

2918

3647

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

516

1032

1548

2064

2580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00648

AC:

987

AN:

152270

Hom.:

Cov.:

AF XY:

0.00600

AC XY:

447

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.00231

AC:

AN:

41528

American (AMR)

AF:

0.00641

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.000415

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00160

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0112

AC:

759

AN:

68024

Other (OTH)

AF:

0.00616

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

149

198

248

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

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

PhyloP100

4.6

PrimateAI

Uncertain

0.60

PROVEAN

Benign

1.5

REVEL

Benign

0.24

Sift

Benign

0.21

Sift4G

Benign

0.21

Vest4

0.53

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

Mutation Taster

=82/18

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over