chr1-44801630-C-A

Variant names:

• chr1-44801630-C-A
• rs140199593
• NM_004073.4:c.444C>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_004073.4(PLK3):​c.444C>A​(p.Ala148Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00374 in 1,613,290 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0022 (1 hom., cov: 29)
  • Exomes 𝑓: 0.0039 (19 hom.)
• Consequence: PLK3 NM_004073.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0960
• 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=-0.35).
• BP6: Variant 1-44801630-C-A is Benign according to our data. Variant chr1-44801630-C-A is described in ClinVar as Benign. ClinVar VariationId is 770845.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.096 with no splicing effect.
• BS2: High AC in GnomAd4 at 336 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.444C>A	p.Ala148Ala	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.444C>A	p.Ala148Ala	synonymous	Exon 4 of 15	ENSP00000361275.4	Q9H4B4
	PLK3	ENST00000854219.1		c.444C>A	p.Ala148Ala	synonymous	Exon 4 of 15	ENSP00000524278.1
	PLK3	ENST00000850614.1		c.444C>A	p.Ala148Ala	synonymous	Exon 4 of 15	ENSP00000520901.1	Q9H4B4

Frequencies

GnomAD3 genomes AF: 0.00221 AC: 336 AN: 151768 Hom.: 1 Cov.: 29

Gnomad AFR AF: 0.000799

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00112

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000946

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00409

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00230 AC: 577 AN: 250392 AF XY: 0.00221

Gnomad AFR exome AF: 0.000740

Gnomad AMR exome AF: 0.00139

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000693

Gnomad NFE exome AF: 0.00435

Gnomad OTH exome AF: 0.00164

GnomAD4 exome AF: 0.00390 AC: 5700 AN: 1461404 Hom.: 19 Cov.: 36 AF XY: 0.00382 AC XY: 2775 AN XY: 727002

African (AFR) AF: 0.000568 AC: 19 AN: 33480

American (AMR) AF: 0.00127 AC: 57 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86252

European-Finnish (FIN) AF: 0.00104 AC: 55 AN: 53114

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00490 AC: 5443 AN: 1111868

Other (OTH) AF: 0.00199 AC: 120 AN: 60378

GnomAD4 genome AF: 0.00221 AC: 336 AN: 151886 Hom.: 1 Cov.: 29 AF XY: 0.00182 AC XY: 135 AN XY: 74242

African (AFR) AF: 0.000797 AC: 33 AN: 41420

American (AMR) AF: 0.00111 AC: 17 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4796

European-Finnish (FIN) AF: 0.0000946 AC: 1 AN: 10574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00409 AC: 278 AN: 67892

Other (OTH) AF: 0.00284 AC: 6 AN: 2110

Alfa AF: 0.00325 Hom.: 0

Bravo AF: 0.00212

EpiCase AF: 0.00436

EpiControl AF: 0.00356

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	13
DANN	Benign	0.84
PhyloP100		0.096
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs140199593; hg19: chr1-45267302;