Variant chr1-44801075-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004073.4(PLK3):c.358C>T(p.Arg120Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,624 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PLK3
NM_004073.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.42

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLK3	NM_004073.4 linkuse as main transcript	c.358C>T	p.Arg120Cys	missense_variant	3/15	ENST00000372201.5	NP_004064.2	Q9H4B4
PLK3	XM_047444455.1 linkuse as main transcript	c.358C>T	p.Arg120Cys	missense_variant	3/13		XP_047300411.1
PLK3	XM_047444463.1 linkuse as main transcript	c.358C>T	p.Arg120Cys	missense_variant	3/9		XP_047300419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLK3	ENST00000372201.5 linkuse as main transcript	c.358C>T	p.Arg120Cys	missense_variant	3/15	1	NM_004073.4	ENSP00000361275.4		Q9H4B4
PLK3	ENST00000465443.5 linkuse as main transcript	n.434C>T		non_coding_transcript_exon_variant	3/14	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250840

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135824

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461624

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727104

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 06, 2021

The c.358C>T (p.R120C) alteration is located in exon 3 (coding exon 3) of the PLK3 gene. This alteration results from a C to T substitution at nucleotide position 358, causing the arginine (R) at amino acid position 120 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.064

BayesDel_noAF

Benign

-0.33

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.49

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.78

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.60

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

PrimateAI

Uncertain

0.59

PROVEAN

Pathogenic

-4.5

REVEL

Benign

0.17

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0030

Polyphen

0.92

Vest4

0.47

MutPred

0.60

Loss of disorder (P = 0.0534);

MVP

0.73

MPC

1.4

ClinPred

0.88

GERP RS

3.9

Varity_R

0.43

gMVP

0.38

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