1-44800486-T-G

Variant names:

• chr1-44800486-T-G
• NM_004073.4:c.23T>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004073.4(PLK3):​c.23T>G​(p.Leu8Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000781 in 1,281,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L8P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
• Consequence: PLK3 NM_004073.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.228

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20163542).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLK3	NM_004073.4	c.23T>G	p.Leu8Arg	missense_variant	Exon 1 of 15	ENST00000372201.5	NP_004064.2
PLK3	XM_047444455.1	c.23T>G	p.Leu8Arg	missense_variant	Exon 1 of 13		XP_047300411.1
PLK3	XM_047444463.1	c.23T>G	p.Leu8Arg	missense_variant	Exon 1 of 9		XP_047300419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLK3	ENST00000372201.5	c.23T>G	p.Leu8Arg	missense_variant	Exon 1 of 15	1	NM_004073.4	ENSP00000361275.4
PLK3	ENST00000465443.5	n.99T>G		non_coding_transcript_exon_variant	Exon 1 of 14	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.81e-7 AC: 1 AN: 1281154 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 631172

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: 9.70e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	19
DANN	Benign	0.56
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.58	T
M_CAP	Pathogenic	0.63	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.75	N
REVEL	Benign	0.13
Sift	Uncertain	0.012	D
Sift4G	Benign	0.46	T
Polyphen		0.13	B
Vest4		0.26
MutPred		0.26		Gain of MoRF binding (P = 0.0018);
MVP		0.68
MPC		0.59
ClinPred		0.094	T
GERP RS		0.12
Varity_R		0.16
gMVP		0.34

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: chr1-45266158;