Genetic Variant CDK10:p.Arg357Leu (chr16-89695679-G-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PM2PM5BP4

The NM_052988.5(CDK10):c.1070G>T(p.Arg357Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. R357H) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CDK10
NM_052988.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.45

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 Gene-Disease associations (from GenCC):

Al Kaissi syndrome
Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)

CDK10 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr16-89695679-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 402152.

BP4

Computational evidence support a benign effect (MetaRNN=0.35893065).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052988.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDK10	NM_052988.5	MANE Select	c.1070G>T	p.Arg357Leu	missense	Exon 13 of 13	NP_443714.3
CDK10	NM_001160367.2		c.857G>T	p.Arg286Leu	missense	Exon 13 of 13	NP_001153839.1	Q15131-2
CDK10	NM_001098533.3		c.839G>T	p.Arg280Leu	missense	Exon 13 of 13	NP_001092003.2	Q15131-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDK10	ENST00000353379.12	TSL:1 MANE Select	c.1070G>T	p.Arg357Leu	missense	Exon 13 of 13	ENSP00000338673.7	Q15131-1
CDK10	ENST00000505473.5	TSL:1	c.773-50G>T		intron	N/A	ENSP00000424415.1	Q15131-4
CDK10	ENST00000851882.1		c.1166G>T	p.Arg389Leu	missense	Exon 13 of 13	ENSP00000521941.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1446482

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

718792

African (AFR)

AF:

0.00

AC:

AN:

33188

American (AMR)

AF:

0.00

AC:

AN:

43402

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25864

East Asian (EAS)

AF:

0.00

AC:

AN:

38986

South Asian (SAS)

AF:

0.00

AC:

AN:

84054

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1106836

Other (OTH)

AF:

0.00

AC:

AN:

59810

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Uncertain

-0.010

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.023

Eigen

Benign

0.12

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.86

M_CAP

Uncertain

0.099

MetaRNN

Benign

0.36

MetaSVM

Benign

-0.69

MutationAssessor

Uncertain

2.2

PhyloP100

7.4

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.6

REVEL

Uncertain

0.38

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.012

Polyphen

0.92

Vest4

0.60

MutPred

0.33

Loss of solvent accessibility (P = 3e-04)

MVP

0.61

MPC

0.57

ClinPred

0.96

GERP RS

4.9

Varity_R

0.42

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over