dbSNP rs1258010770: CDK10:p.Lys14Thr (chr16-89686751-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_052988.5(CDK10):c.41A>C(p.Lys14Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,284 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict 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. K14R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CDK10
NM_052988.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.99

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20235187).

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.41A>C	p.Lys14Thr	missense	Exon 1 of 13	NP_443714.3
CDK10	NM_001160367.2		c.-135A>C		5_prime_UTR	Exon 1 of 13	NP_001153839.1	Q15131-2
CDK10	NM_001098533.3		c.-135A>C		5_prime_UTR	Exon 1 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.41A>C	p.Lys14Thr	missense	Exon 1 of 13	ENSP00000338673.7	Q15131-1
CDK10	ENST00000505473.5	TSL:1	c.-135A>C		5_prime_UTR	Exon 1 of 13	ENSP00000424415.1	Q15131-4
CDK10	ENST00000851882.1		c.41A>C	p.Lys14Thr	missense	Exon 1 of 13	ENSP00000521941.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000409

AC:

AN:

244580

AF XY:

0.00000749

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000292

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:

6.85e-7

AC:

AN:

1460284

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726450

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33426

American (AMR)

AF:

0.0000224

AC:

AN:

44634

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26086

East Asian (EAS)

AF:

0.00

AC:

AN:

39646

South Asian (SAS)

AF:

0.00

AC:

AN:

86138

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53078

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111220

Other (OTH)

AF:

0.00

AC:

AN:

60290

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.011

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0073

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.81

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.81

PhyloP100

2.0

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

0.44

REVEL

Benign

0.15

Sift

Benign

0.17

Sift4G

Benign

0.34

Polyphen

0.0010

Vest4

0.47

MutPred

0.44

Loss of methylation at K14 (P = 0.0064)

MVP

0.61

MPC

0.12

ClinPred

0.26

GERP RS

4.5

PromoterAI

0.079

Neutral

(source)

Varity_R

0.16

gMVP

0.64

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

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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