Variant chrX-47223642-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_006201.5(CDK16):c.85G>A(p.Glu29Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000413 in 1,209,659 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.0000036 ( 0 hom. 1 hem. )

Consequence

CDK16
NM_006201.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.34

Variant links:

Genes affected

CDK16 (HGNC:8749): (cyclin dependent kinase 16) The protein encoded by this gene belongs to the cdc2/cdkx subfamily of the ser/thr family of protein kinases. It may play a role in signal transduction cascades in terminally differentiated cells; in exocytosis; and in transport of secretory cargo from the endoplasmic reticulum. This gene is thought to escape X inactivation. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2009]

CDK16 links:

CDK16 (HGNC:):

CDK16 links:

Genome browser will be placed here

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=0.36498713).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK16	NM_006201.5 linkuse as main transcript	c.85G>A	p.Glu29Lys	missense_variant	2/16	ENST00000357227.9	NP_006192.1	Q00536-1A0A140VK97Q9BRL4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK16	ENST00000357227.9 linkuse as main transcript	c.85G>A	p.Glu29Lys	missense_variant	2/16	1	NM_006201.5	ENSP00000349762.4		Q00536-1

Frequencies

GnomAD3 genomes

AF:

0.00000894

AC:

AN:

111823

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33983

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000364

AC:

AN:

1097836

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363196

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:

0.00000356

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.00000894

AC:

AN:

111823

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33983

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

May 04, 2022

The c.307G>A (p.E103K) alteration is located in exon 2 (coding exon 2) of the CDK16 gene. This alteration results from a G to A substitution at nucleotide position 307, causing the glutamic acid (E) at amino acid position 103 to be replaced by a lysine (K). 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

Uncertain

0.40

BayesDel_addAF

Uncertain

0.044

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.080

.;T;T;T;T;.;T;T;.

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

D;D;.;D;D;D;D;D;D

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.36

T;T;T;T;T;T;T;T;T

MetaSVM

Uncertain

-0.21

MutationAssessor

Uncertain

2.6

.;.;M;.;.;.;.;M;.

MutationTaster

Benign

0.95

D;D;D;D

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.5

N;D;N;N;N;N;N;N;N

REVEL

Benign

0.27

Sift

Uncertain

0.0080

D;D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.045

D;D;T;D;D;D;D;T;D

Polyphen

0.86

.;.;P;.;.;.;.;P;.

Vest4

0.48

MutPred

0.22

.;Gain of ubiquitination at E29 (P = 0.0018);Gain of ubiquitination at E29 (P = 0.0018);Gain of ubiquitination at E29 (P = 0.0018);Gain of ubiquitination at E29 (P = 0.0018);Gain of ubiquitination at E29 (P = 0.0018);Gain of ubiquitination at E29 (P = 0.0018);Gain of ubiquitination at E29 (P = 0.0018);.;

MVP

0.84

MPC

1.1

ClinPred

0.94

GERP RS

4.3

Varity_R

0.35

gMVP

0.54

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