Genetic Variant CDK13:p.Ser33Thr (chr7-39950738-T-A) – 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_003718.5(CDK13):c.97T>A(p.Ser33Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000759 in 1,317,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. S33P) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.6e-7 ( 0 hom. )

Consequence

CDK13
NM_003718.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.49

Publications

0 publications found

Variant links:

Genes affected

CDK13 (HGNC:1733): (cyclin dependent kinase 13) The protein encoded by this gene is a member of the cyclin-dependent serine/threonine protein kinase family. Members of this family are well known for their essential roles as master switches in cell cycle control. The exact function of this protein has not yet been determined, but it may play a role in mRNA processing and may be involved in regulation of hematopoiesis. Alternatively spliced transcript variants have been described.[provided by RefSeq, Dec 2009]

CDK13 Gene-Disease associations (from GenCC):

congenital heart defects, dysmorphic facial features, and intellectual developmental disorder
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Illumina
syndromic intellectual disability
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

CDK13 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=0.09391552).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK13	NM_003718.5 link	c.97T>A	p.Ser33Thr	missense_variant	Exon 1 of 14	ENST00000181839.10	NP_003709.3	Q14004-1A0A024RA85Q9BVE2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK13	ENST00000181839.10 link	c.97T>A	p.Ser33Thr	missense_variant	Exon 1 of 14	1	NM_003718.5	ENSP00000181839.4		Q14004-1
CDK13	ENST00000340829.10 link	c.97T>A	p.Ser33Thr	missense_variant	Exon 1 of 14	1		ENSP00000340557.5		Q14004-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.59e-7

AC:

AN:

1317944

Hom.:

Cov.:

AF XY:

0.00000154

AC XY:

AN XY:

649954

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26466

American (AMR)

AF:

0.00

AC:

AN:

24302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23060

East Asian (EAS)

AF:

0.00

AC:

AN:

28562

South Asian (SAS)

AF:

0.00

AC:

AN:

71928

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34484

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3898

European-Non Finnish (NFE)

AF:

9.52e-7

AC:

AN:

1050566

Other (OTH)

AF:

0.00

AC:

AN:

54678

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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

Benign

0.094

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Uncertain

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.085

T;.

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.50

T;T

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.094

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

N;N

PhyloP100

1.5

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-0.26

N;N

REVEL

Benign

0.053

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.14

T;T

Polyphen

0.010

B;B

Vest4

0.097

MutPred

0.080

Loss of MoRF binding (P = 0.1283);Loss of MoRF binding (P = 0.1283);

MVP

0.21

MPC

1.6

ClinPred

0.60

GERP RS

3.6

PromoterAI

-0.098

Neutral

(source)

Varity_R

0.39

gMVP

0.34

Mutation Taster

=96/4

polymorphism

(source)

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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7-39950738-T-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over