Genetic Variant CDKL3:p.Ser501Gly (chr5-134304525-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001113575.2(CDKL3):c.1501A>G(p.Ser501Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

CDKL3
NM_001113575.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.92

Variant links:

Genes affected

CDKL3 (HGNC:15483): (cyclin dependent kinase like 3) The protein encoded by this gene is a member of cyclin-dependent protein kinase (CDK) family. CDK family members are highly similar to the gene products of Saccharomyces cerevisiae cdc28, and Schizosaccharomyces pombe cdc2, and are known to be important regulators of cell cycle progression. This gene was identified as a gene absent in leukemic patients with chromosome 5q deletion. This loss may be an important determinant of dysmyelopoiesis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

CDKL3 links:

ENSG00000273345 (HGNC:):

ENSG00000273345 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14045).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKL3	NM_001113575.2 link	c.1501A>G	p.Ser501Gly	missense_variant	Exon 11 of 13	ENST00000265334.9	NP_001107047.1	Q8IVW4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKL3	ENST00000265334.9 link	c.1501A>G	p.Ser501Gly	missense_variant	Exon 11 of 13	1	NM_001113575.2	ENSP00000265334.4		Q8IVW4-1
ENSG00000273345	ENST00000703317.1 link	n.86-1838A>G		intron_variant	Intron 2 of 9			ENSP00000515260.1		A0A8V8TQA6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1501A>G (p.S501G) alteration is located in exon 11 (coding exon 10) of the CDKL3 gene. This alteration results from a A to G substitution at nucleotide position 1501, causing the serine (S) at amino acid position 501 to be replaced by a glycine (G). 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

Benign

0.062

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.010

T;.;.

Eigen

Benign

-0.00077

Eigen_PC

Benign

0.14

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.72

T;T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

1.7

L;.;.

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.65

N;N;N

REVEL

Benign

0.035

Sift

Benign

0.071

T;D;T

Sift4G

Benign

0.43

T;T;T

Polyphen

0.10

B;B;.

Vest4

0.21

MutPred

0.17

Loss of phosphorylation at S501 (P = 0.0474);.;Loss of phosphorylation at S501 (P = 0.0474);

MVP

0.61

MPC

0.022

ClinPred

0.47

GERP RS

4.6

Varity_R

0.15

gMVP

0.046

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over