Variant 1-44801723-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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:

PLK3 (HGNC:):

PLK3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLK3	NM_004073.4 linkuse as main transcript	c.537C>T	p.Arg179Arg	synonymous_variant	4/15	ENST00000372201.5	NP_004064.2	Q9H4B4
PLK3	XM_047444455.1 linkuse as main transcript	c.537C>T	p.Arg179Arg	synonymous_variant	4/13		XP_047300411.1
PLK3	XM_047444463.1 linkuse as main transcript	c.537C>T	p.Arg179Arg	synonymous_variant	4/9		XP_047300419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PLK3	ENST00000372201.5 linkuse as main transcript	c.537C>T	p.Arg179Arg	synonymous_variant	4/15	1	NM_004073.4	ENSP00000361275.4	Q9H4B4
PLK3	ENST00000465443.5 linkuse as main transcript	n.613C>T		non_coding_transcript_exon_variant	4/14	5
PLK3	ENST00000476731.1 linkuse as main transcript	n.90C>T		non_coding_transcript_exon_variant	1/5	5

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

GnomAD3 exomes

AF:

0.000887

AC:

223

AN:

251350

Hom.:

AF XY:

0.00125

AC XY:

170

AN XY:

135892

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 SAS exome

AF:

0.00536

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

Gnomad4 AFR exome

AF:

0.0000322

Gnomad4 AMR exome

AF:

0.000167

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000308

Gnomad4 SAS exome

AF:

0.00593

Gnomad4 FIN exome

AF:

0.0000215

Gnomad4 NFE exome

AF:

0.000166

Gnomad4 OTH exome

AF:

0.000569

GnomAD4 genome

AF:

0.000331

AC:

AN:

136020

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

AN XY:

65162

show subpopulations

Gnomad4 AFR

AF:

0.0000270

Gnomad4 AMR

AF:

0.000237

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00712

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000187

Gnomad4 OTH

AF:

0.000524

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

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.88

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over