16-23683990-C-T

Variant names:

• chr16-23683990-C-T
• rs145066711
• NM_005030.6:c.937C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_005030.6(PLK1):​c.937C>T​(p.Arg313Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,614,058 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R313S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: PLK1 NM_005030.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.43
• Publications: 0 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.34851348).
• BS2: High AC in GnomAdExome4 at 29 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLK1	NM_005030.6	MANE Select	c.937C>T	p.Arg313Cys	missense	Exon 5 of 10	NP_005021.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLK1	ENST00000300093.9	TSL:1 MANE Select	c.937C>T	p.Arg313Cys	missense	Exon 5 of 10	ENSP00000300093.4	P53350
	PLK1	ENST00000885692.1		c.937C>T	p.Arg313Cys	missense	Exon 5 of 10	ENSP00000555751.1
	PLK1	ENST00000567897.6	TSL:3	c.217C>T	p.Arg73Cys	missense	Exon 5 of 5	ENSP00000459688.1	I3L2H5

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152188 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000398 AC: 10 AN: 251492 AF XY: 0.0000662

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000496

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000439

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000198 AC: 29 AN: 1461870 Hom.: 0 Cov.: 32 AF XY: 0.0000248 AC XY: 18 AN XY: 727238

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000803 AC: 21 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111988

Other (OTH) AF: 0.0000331 AC: 2 AN: 60396

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152188 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74346

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15278

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000303 Hom.: 0

Bravo AF: 0.0000378

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.0000576 AC: 7

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.43	T
Eigen	Uncertain	0.32
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		3.4
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.26
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.017	D
Polyphen		1.0	D
Vest4		0.88
MVP		0.51
MPC		0.56
ClinPred		0.94	D
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.60
gMVP		0.71
Mutation Taster		=81/19	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: rs145066711; hg19: chr16-23695311;