Genetic Variant CDK3:p.Val154Leu (chr17-76002392-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001258.4(CDK3):c.460G>T(p.Val154Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,308 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.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CDK3
NM_001258.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.84

Variant links:

Genes affected

CDK3 (HGNC:1772): (cyclin dependent kinase 3) This gene encodes a member of the cyclin-dependent protein kinase family. The protein promotes entry into S phase, in part by activating members of the E2F family of transcription factors. The protein also associates with cyclin C and phosphorylates the retinoblastoma 1 protein to promote exit from G0. [provided by RefSeq, Jul 2008]

CDK3 links:

TEN1-CDK3 (HGNC:44420): (TEN1-CDK3 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring TEN1 telomerase capping complex subunit homolog (S. cerevisiae) and cyclin-dependent kinase 3 (CDK3) genes. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is therefore unlikely to produce a protein product. [provided by RefSeq, Oct 2011]

TEN1-CDK3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40171203).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK3	NM_001258.4 link	c.460G>T	p.Val154Leu	missense_variant	Exon 5 of 8	ENST00000448471.3	NP_001249.1	Q00526
TEN1-CDK3	NR_037709.1 link	n.2296G>T		non_coding_transcript_exon_variant	Exon 7 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CDK3	ENST00000448471.3 link	c.460G>T	p.Val154Leu	missense_variant	Exon 5 of 8	5	NM_001258.4	ENSP00000400088.1	Q00526
TEN1-CDK3	ENST00000649294.1 link	n.*601G>T		non_coding_transcript_exon_variant	Exon 8 of 11			ENSP00000497034.1
TEN1-CDK3	ENST00000649294.1 link	n.*601G>T		3_prime_UTR_variant	Exon 8 of 11			ENSP00000497034.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460308

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726464

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Uncertain

0.088

BayesDel_noAF

Benign

-0.11

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

T;T;T;.

Eigen

Benign

-0.088

Eigen_PC

Benign

0.13

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

D;T;.;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.40

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.26

.;N;N;.

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.92

.;N;N;.

REVEL

Uncertain

0.31

Sift

Benign

0.13

.;T;T;.

Sift4G

Benign

0.11

T;T;T;T

Polyphen

0.026

.;B;B;.

Vest4

0.76

MutPred

0.47

Gain of methylation at R150 (P = 0.1505);Gain of methylation at R150 (P = 0.1505);Gain of methylation at R150 (P = 0.1505);.;

MVP

0.33

MPC

0.41

ClinPred

0.86

GERP RS

4.5

Varity_R

0.20

gMVP

0.39

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over