Genetic Variant NM_004073.4:c.537C>T (chr1-44801723-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_004073.4(PLK3):c.537C>T(p.Arg179Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000514 in 1,508,684 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 28)

Exomes 𝑓: 0.00053 ( 10 hom. )

Consequence

PLK3
NM_004073.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0980

Publications

0 publications found

Variant links:

Genes affected

PLK3 (HGNC:2154): (polo like kinase 3) The protein encoded by this gene is a member of the highly conserved polo-like kinase family of serine/threonine kinases. Members of this family are characterized by an amino-terminal kinase domain and a carboxy-terminal bipartite polo box domain that functions as a substrate-binding motif and a cellular localization signal. Polo-like kinases are important regulators of cell cycle progression. This gene has also been implicated in stress responses and double-strand break repair. In human cell lines, this protein is reported to associate with centrosomes in a microtubule-dependent manner, and during mitosis, the protein becomes localized to the mitotic apparatus. Expression of a kinase-defective mutant results in abnormal cell morphology caused by changes in microtubule dynamics and mitotic arrest followed by apoptosis. [provided by RefSeq, Sep 2015]

PLK3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 1-44801723-C-T is Benign according to our data. Variant chr1-44801723-C-T is described in ClinVar as Benign. ClinVar VariationId is 775133.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.098 with no splicing effect.

BS2

High AC in GnomAd4 at 45 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004073.4. 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
	PLK3	NM_004073.4	MANE Select	c.537C>T	p.Arg179Arg	synonymous	Exon 4 of 15	NP_004064.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLK3	ENST00000372201.5	TSL:1 MANE Select	c.537C>T	p.Arg179Arg	synonymous	Exon 4 of 15	ENSP00000361275.4	Q9H4B4
PLK3	ENST00000854219.1		c.537C>T	p.Arg179Arg	synonymous	Exon 4 of 15	ENSP00000524278.1
PLK3	ENST00000850614.1		c.537C>T	p.Arg179Arg	synonymous	Exon 4 of 15	ENSP00000520901.1	Q9H4B4

Frequencies

GnomAD3 genomes

AF:

0.000331

AC:

AN:

135942

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000270

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000237

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00712

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000187

Gnomad OTH

AF:

0.000528

GnomAD2 exomes

AF:

0.000887

AC:

223

AN:

251350

AF XY:

0.00125

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000414

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000532

AC:

730

AN:

1372664

Hom.:

Cov.:

AF XY:

0.000760

AC XY:

518

AN XY:

681480

show subpopulations

African (AFR)

AF:

0.0000322

AC:

AN:

31048

American (AMR)

AF:

0.000167

AC:

AN:

41960

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22848

East Asian (EAS)

AF:

0.0000308

AC:

AN:

32458

South Asian (SAS)

AF:

0.00593

AC:

506

AN:

85392

European-Finnish (FIN)

AF:

0.0000215

AC:

AN:

46510

Middle Eastern (MID)

AF:

0.00151

AC:

AN:

5290

European-Non Finnish (NFE)

AF:

0.000166

AC:

175

AN:

1052660

Other (OTH)

AF:

0.000569

AC:

AN:

54498

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

134

178

223

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.000331

AC:

AN:

136020

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

AN XY:

65162

show subpopulations

African (AFR)

AF:

0.0000270

AC:

AN:

37072

American (AMR)

AF:

0.000237

AC:

AN:

12660

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3318

East Asian (EAS)

AF:

0.00

AC:

AN:

4048

South Asian (SAS)

AF:

0.00712

AC:

AN:

3932

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7638

Middle Eastern (MID)

AF:

0.00

AC:

AN:

272

European-Non Finnish (NFE)

AF:

0.000187

AC:

AN:

64298

Other (OTH)

AF:

0.000524

AC:

AN:

1910

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.552

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000131

Hom.:

Bravo

AF:

0.000208

Asia WGS

AF:

0.00173

AC:

AN:

3476

EpiCase

AF:

0.000164

EpiControl

AF:

0.000356

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.88

PhyloP100

-0.098

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over