Variant 1-1704651-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_024011.4(CDK11A):c.1463T>C(p.Ile488Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000651 in 1,596,448 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 1 hom., cov: 31)

Exomes 𝑓: 0.000047 ( 3 hom. )

Consequence

CDK11A
NM_024011.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.57

Variant links:

Genes affected

CDK11A (HGNC:1730): (cyclin dependent kinase 11A) This gene encodes a member of the serine/threonine protein kinase family. Members of this kinase family are known to be essential for eukaryotic cell cycle control. Due to a segmental duplication, this gene shares very high sequence identity with a neighboring gene. These two genes are frequently deleted or altered in neuroblastoma. The protein kinase encoded by this gene can be cleaved by caspases and may play a role in cell apoptosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

CDK11A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK11A	NM_024011.4 linkuse as main transcript	c.1463T>C	p.Ile488Thr	missense_variant	14/20	ENST00000404249.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK11A	ENST00000404249.8 linkuse as main transcript	c.1463T>C	p.Ile488Thr	missense_variant	14/20	1	NM_024011.4	P1	Q9UQ88-2

Frequencies

GnomAD3 genomes

AF:

0.000240

AC:

AN:

150300

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000811

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000663

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000296

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000707

AC:

AN:

226390

Hom.:

AF XY:

0.0000569

AC XY:

AN XY:

122946

show subpopulations

Gnomad AFR exome

AF:

0.000956

Gnomad AMR exome

AF:

0.0000310

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000392

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000470

AC:

AN:

1446148

Hom.:

Cov.:

AF XY:

0.0000515

AC XY:

AN XY:

718404

show subpopulations

Gnomad4 AFR exome

AF:

0.000705

Gnomad4 AMR exome

AF:

0.0000466

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000237

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000335

Gnomad4 OTH exome

AF:

0.0000669

GnomAD4 genome

AF:

0.000240

AC:

AN:

150300

Hom.:

Cov.:

AF XY:

0.000232

AC XY:

AN XY:

73306

show subpopulations

Gnomad4 AFR

AF:

0.000811

Gnomad4 AMR

AF:

0.0000663

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000296

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000428

Hom.:

Bravo

AF:

0.000329

ESP6500AA

AF:

0.00134

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000833

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 22, 2021

The c.1463T>C (p.I488T) alteration is located in exon 14 (coding exon 13) of the CDK11A gene. This alteration results from a T to C substitution at nucleotide position 1463, causing the isoleucine (I) at amino acid position 488 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Uncertain

-0.070

Cadd

Uncertain

Dann

Uncertain

0.98

Eigen

Benign

0.17

Eigen_PC

Benign

0.083

FATHMM_MKL

Benign

0.55

M_CAP

Benign

0.079

MetaRNN

Uncertain

0.52

D;D;D;D;D;D

MetaSVM

Benign

-0.53

MutationTaster

Benign

1.0

D;D;D;D;D;D

PROVEAN

Pathogenic

-4.5

D;D;D;D;D;D

REVEL

Uncertain

0.43

Sift

Pathogenic

0.0

D;D;D;D;D;D

Sift4G

Uncertain

0.0020

D;D;D;D;D;D

Polyphen

0.96

.;.;D;.;D;.

Vest4

0.77

MVP

0.81

MPC

0.24

ClinPred

0.24

GERP RS

2.2

Varity_R

0.71

gMVP

0.72

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over