NM_005030.6:c.1263C>T

Variant names:

• chr16-23688738-C-T
• rs2230914
• NM_005030.6:c.1263C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_005030.6(PLK1):​c.1263C>T​(p.Tyr421Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 1,611,596 control chromosomes in the GnomAD database, including 1,064 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 0.050 (541 hom., cov: 33)
  • Exomes 𝑓: 0.011 (523 hom.)
• Consequence: PLK1 NM_005030.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.272
• Publications: 7 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP7: Synonymous conserved (PhyloP=-0.272 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

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.1263C>T	p.Tyr421Tyr	synonymous	Exon 7 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.1263C>T	p.Tyr421Tyr	synonymous	Exon 7 of 10	ENSP00000300093.4	P53350
	PLK1	ENST00000885692.1		c.1263C>T	p.Tyr421Tyr	synonymous	Exon 7 of 10	ENSP00000555751.1
	PLK1	ENST00000922967.1		c.804C>T	p.Tyr268Tyr	synonymous	Exon 4 of 7	ENSP00000593026.1

Frequencies

GnomAD3 genomes AF: 0.0501 AC: 7626 AN: 152192 Hom.: 529 Cov.: 33

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0219

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00640

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00800

Gnomad OTH AF: 0.0392

GnomAD2 exomes AF: 0.0166 AC: 4181 AN: 251458 AF XY: 0.0135

Gnomad AFR exome AF: 0.163

Gnomad AMR exome AF: 0.00974

Gnomad ASJ exome AF: 0.00149

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00573

Gnomad NFE exome AF: 0.00811

Gnomad OTH exome AF: 0.0122

GnomAD4 exome AF: 0.0112 AC: 16278 AN: 1459286 Hom.: 523 Cov.: 30 AF XY: 0.0103 AC XY: 7513 AN XY: 726152

African (AFR) AF: 0.161 AC: 5372 AN: 33380

American (AMR) AF: 0.0110 AC: 491 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00123 AC: 32 AN: 26116

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39696

South Asian (SAS) AF: 0.00204 AC: 176 AN: 86208

European-Finnish (FIN) AF: 0.00607 AC: 324 AN: 53418

Middle Eastern (MID) AF: 0.0144 AC: 83 AN: 5762

European-Non Finnish (NFE) AF: 0.00790 AC: 8772 AN: 1109714

Other (OTH) AF: 0.0170 AC: 1026 AN: 60276

GnomAD4 genome AF: 0.0504 AC: 7670 AN: 152310 Hom.: 541 Cov.: 33 AF XY: 0.0494 AC XY: 3678 AN XY: 74488

African (AFR) AF: 0.159 AC: 6626 AN: 41554

American (AMR) AF: 0.0219 AC: 335 AN: 15310

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

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4828

European-Finnish (FIN) AF: 0.00640 AC: 68 AN: 10628

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00800 AC: 544 AN: 68014

Other (OTH) AF: 0.0388 AC: 82 AN: 2112

Alfa AF: 0.0278 Hom.: 122

Bravo AF: 0.0558

Asia WGS AF: 0.0140 AC: 50 AN: 3478

EpiCase AF: 0.00714

EpiControl AF: 0.00646

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	8.8
DANN	Benign	0.86
PhyloP100		-0.27
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2230914; hg19: chr16-23700059;