5-134308579-C-T

Variant names:

• chr5-134308579-C-T
• rs1384434874
• NM_001113575.2:c.1030G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001113575.2(CDKL3):​c.1030G>A​(p.Gly344Arg) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDKL3 NM_001113575.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.96
• Publications: 0 publications found

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]

ENSG00000273345 (HGNC:):

ACMG classification

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=0.24948397).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001113575.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKL3	NM_001113575.2	MANE Select	c.1030G>A	p.Gly344Arg	missense	Exon 8 of 13	NP_001107047.1	Q8IVW4-1
	CDKL3	NM_016508.4		c.1030G>A	p.Gly344Arg	missense	Exon 8 of 9	NP_057592.2	Q8IVW4-2
	CDKL3	NM_001349363.2		c.463G>A	p.Gly155Arg	missense	Exon 5 of 11	NP_001336292.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKL3	ENST00000265334.9	TSL:1 MANE Select	c.1030G>A	p.Gly344Arg	missense	Exon 8 of 13	ENSP00000265334.4	Q8IVW4-1
	CDKL3	ENST00000523832.1	TSL:1	c.1030G>A	p.Gly344Arg	missense	Exon 7 of 8	ENSP00000430496.1	Q8IVW4-2
	CDKL3	ENST00000519312.5	TSL:1	n.315-113G>A		intron	N/A	ENSP00000427738.1	E5RGK4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.052	T
Eigen	Benign	0.18
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.083	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.0
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.20
Sift	Benign	0.031	D
Sift4G	Benign	0.32	T
Polyphen		0.81	P
Vest4		0.29
MutPred		0.20		Gain of MoRF binding (P = 0.0077)
MVP		0.72
MPC		0.022
ClinPred		0.79	D
GERP RS		4.8
Varity_R		0.13
gMVP		0.20
Mutation Taster		=51/49	polymorphism

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

Other links and lift over

dbSNP: rs1384434874; hg19: chr5-133644270;