16-23689355-T-A

Variant names:

• chr16-23689355-T-A
• rs45569335
• NM_005030.6:c.1388T>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.59
• Publications: 14 publications found

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005030.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLK1	NM_005030.6	MANE Select	c.1388T>A	p.Leu463His	missense	Exon 8 of 10	NP_005021.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLK1	ENST00000300093.9	TSL:1 MANE Select	c.1388T>A	p.Leu463His	missense	Exon 8 of 10	ENSP00000300093.4
	PLK1	ENST00000562272.5	TSL:2	n.3408T>A		non_coding_transcript_exon	Exon 7 of 9
	PLK1	ENST00000564794.1	TSL:5	n.188T>A		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes AF: 0.00649 AC: 987 AN: 152152 Hom.: 4 Cov.: 32

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

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.: 95 Cov.: 32 AF XY: 0.00959 AC XY: 6968 AN XY: 726390

African (AFR) AF: 0.00158 AC: 53 AN: 33468

American (AMR) AF: 0.00465 AC: 208 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26130

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39634

South Asian (SAS) AF: 0.000429 AC: 37 AN: 86230

European-Finnish (FIN) AF: 0.00253 AC: 135 AN: 53412

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5766

European-Non Finnish (NFE) AF: 0.0123 AC: 13702 AN: 1110992

Other (OTH) AF: 0.00663 AC: 400 AN: 60350

GnomAD4 genome AF: 0.00648 AC: 987 AN: 152270 Hom.: 4 Cov.: 32 AF XY: 0.00600 AC XY: 447 AN XY: 74452

African (AFR) AF: 0.00231 AC: 96 AN: 41528

American (AMR) AF: 0.00641 AC: 98 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.00160 AC: 17 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0112 AC: 759 AN: 68024

Other (OTH) AF: 0.00616 AC: 13 AN: 2112

Alfa AF: 0.00919 Hom.: 4

Bravo AF: 0.00693

TwinsUK AF: 0.0116 AC: 43

ALSPAC AF: 0.0125 AC: 48

ESP6500AA AF: 0.00341 AC: 15

ESP6500EA AF: 0.0100 AC: 86

ExAC AF: 0.00630 AC: 765

Asia WGS AF: 0.000866 AC: 4 AN: 3478

EpiCase AF: 0.00867

EpiControl AF: 0.00806

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	22
DANN	Benign	0.92
DEOGEN2	Benign	0.044	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.031
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.78	T
MetaRNN	Benign	0.0088	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.050	N
PhyloP100		4.6
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	1.5	N
REVEL	Benign	0.24
Sift	Benign	0.21	T
Sift4G	Benign	0.21	T
Polyphen		0.0010	B
Vest4		0.53
MVP		0.82
MPC		1.0
ClinPred		0.018	T
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

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

Other links and lift over

dbSNP: rs45569335; hg19: chr16-23700676; COSMIC: COSV99892663; COSMIC: COSV99892663;