1-44801070-A-T

Variant summary

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

The NM_004073.4(PLK3):​c.353A>T​(p.Gln118Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

PLK3
NM_004073.4 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.90
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]

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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
PLK3NM_004073.4 linkc.353A>T p.Gln118Leu missense_variant 3/15 ENST00000372201.5 NP_004064.2 Q9H4B4
PLK3XM_047444455.1 linkc.353A>T p.Gln118Leu missense_variant 3/13 XP_047300411.1
PLK3XM_047444463.1 linkc.353A>T p.Gln118Leu missense_variant 3/9 XP_047300419.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PLK3ENST00000372201.5 linkc.353A>T p.Gln118Leu missense_variant 3/151 NM_004073.4 ENSP00000361275.4 Q9H4B4
PLK3ENST00000465443.5 linkn.429A>T non_coding_transcript_exon_variant 3/145

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
31

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 submitterclinical testingAmbry GeneticsMar 29, 2024The c.353A>T (p.Q118L) alteration is located in exon 3 (coding exon 3) of the PLK3 gene. This alteration results from a A to T substitution at nucleotide position 353, causing the glutamine (Q) at amino acid position 118 to be replaced by a leucine (L). 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
0.16
BayesDel_addAF
Benign
-0.094
T
BayesDel_noAF
Benign
-0.37
CADD
Uncertain
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.36
T
Eigen
Benign
-0.098
Eigen_PC
Benign
0.087
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Uncertain
0.90
D
M_CAP
Benign
0.011
T
MetaRNN
Uncertain
0.55
D
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.7
L
PrimateAI
Benign
0.41
T
PROVEAN
Uncertain
-3.0
D
REVEL
Benign
0.14
Sift
Benign
0.12
T
Sift4G
Benign
0.31
T
Polyphen
0.063
B
Vest4
0.45
MutPred
0.50
Loss of disorder (P = 0.091);
MVP
0.78
MPC
0.45
ClinPred
0.93
D
GERP RS
4.9
Varity_R
0.35
gMVP
0.40

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-45266742; API