1-44801723-C-A

Variant names:

• chr1-44801723-C-A
• rs142337193
• NM_004073.4:c.537C>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_004073.4(PLK3):​c.537C>A​(p.Arg179Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000994 in 1,508,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R179R) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0000074 (0 hom., cov: 28)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: PLK3 NM_004073.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0980
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP7: Synonymous conserved (PhyloP=-0.098 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 14 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>A	p.Arg179Arg	synonymous	Exon 4 of 15	NP_004064.2

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.00000736 AC: 1 AN: 135942 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000156

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000102 AC: 14 AN: 1372664 Hom.: 0 Cov.: 37 AF XY: 0.0000117 AC XY: 8 AN XY: 681480

African (AFR) AF: 0.00 AC: 0 AN: 31048

American (AMR) AF: 0.00 AC: 0 AN: 41960

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22848

East Asian (EAS) AF: 0.00 AC: 0 AN: 32458

South Asian (SAS) AF: 0.00 AC: 0 AN: 85392

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46510

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5290

European-Non Finnish (NFE) AF: 0.0000133 AC: 14 AN: 1052660

Other (OTH) AF: 0.00 AC: 0 AN: 54498

GnomAD4 genome AF: 0.00000736 AC: 1 AN: 135942 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 65092

African (AFR) AF: 0.00 AC: 0 AN: 37002

American (AMR) AF: 0.00 AC: 0 AN: 12642

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3318

East Asian (EAS) AF: 0.00 AC: 0 AN: 4052

South Asian (SAS) AF: 0.00 AC: 0 AN: 3932

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7638

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000156 AC: 1 AN: 64300

Other (OTH) AF: 0.00 AC: 0 AN: 1894

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	7.0
DANN	Benign	0.84
PhyloP100		-0.098
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs142337193; hg19: chr1-45267395;