Genetic Variant CDK10:p.Arg29Thr (chr16-89686796-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_052988.5(CDK10):c.86G>C(p.Arg29Thr) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000687 in 1,456,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. R29K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CDK10
NM_052988.5 missense, splice_region

Scores

Splicing: ADA: 0.7875

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.74

Publications

0 publications found

Variant links:

Genes affected

CDK10 (HGNC:1770): (cyclin dependent kinase 10) The protein encoded by this gene belongs to the CDK subfamily of the Ser/Thr protein kinase family. The CDK subfamily members are highly similar to the gene products of S. cerevisiae cdc28, and S. pombe cdc2, and are known to be essential for cell cycle progression. This kinase has been shown to play a role in cellular proliferation and its function is limited to cell cycle G2-M phase. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

CDK10 links:

LINC02166 (HGNC:53027): (long intergenic non-protein coding RNA 2166)

LINC02166 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38622174).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK10	NM_052988.5 link	c.86G>C	p.Arg29Thr	missense_variant, splice_region_variant	Exon 1 of 13	ENST00000353379.12	NP_443714.3	Q15131-1B7Z537

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK10	ENST00000353379.12 link	c.86G>C	p.Arg29Thr	missense_variant, splice_region_variant	Exon 1 of 13	1	NM_052988.5	ENSP00000338673.7		Q15131-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000426

AC:

AN:

234922

AF XY:

0.00000777

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1456134

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724294

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33304

American (AMR)

AF:

0.00

AC:

AN:

44274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25984

East Asian (EAS)

AF:

0.00

AC:

AN:

39334

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85740

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52448

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109236

Other (OTH)

AF:

0.00

AC:

AN:

60060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Uncertain

0.026

BayesDel_noAF

Benign

-0.10

CADD

Uncertain

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.0090

T;T

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.052

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.87

D;T

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.39

T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

0.97

L;.

PhyloP100

3.7

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.80

N;.

REVEL

Benign

0.21

Sift

Benign

0.55

T;.

Sift4G

Benign

0.51

T;D

Polyphen

0.14

B;.

Vest4

0.63

MutPred

0.43

Gain of phosphorylation at R29 (P = 0.0197);Gain of phosphorylation at R29 (P = 0.0197);

MVP

0.51

MPC

0.15

ClinPred

0.45

GERP RS

4.2

PromoterAI

0.038

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.35

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.79

dbscSNV1_RF

Benign

0.63

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over