NM_001113575.2:c.1390C>T

Variant names:

• chr5-134306677-G-A
• rs550312225
• NM_001113575.2:c.1390C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001113575.2(CDKL3):​c.1390C>T​(p.Arg464Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000146 in 1,563,788 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00015 (1 hom.)
• Consequence: CDKL3 NM_001113575.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.567
• Publications: 7 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.049702168).

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.1390C>T	p.Arg464Cys	missense	Exon 10 of 13	NP_001107047.1	Q8IVW4-1
	CDKL3	NM_001349363.2		c.823C>T	p.Arg275Cys	missense	Exon 7 of 11	NP_001336292.1
	CDKL3	NM_001300853.2		c.823C>T	p.Arg275Cys	missense	Exon 9 of 13	NP_001287782.1	B4DX41

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKL3	ENST00000265334.9	TSL:1 MANE Select	c.1390C>T	p.Arg464Cys	missense	Exon 10 of 13	ENSP00000265334.4	Q8IVW4-1
	CDKL3	ENST00000519312.5	TSL:1	n.*348C>T		non_coding_transcript_exon	Exon 6 of 9	ENSP00000427738.1	E5RGK4
	CDKL3	ENST00000519312.5	TSL:1	n.*348C>T		3_prime_UTR	Exon 6 of 9	ENSP00000427738.1	E5RGK4

Frequencies

GnomAD3 genomes AF: 0.000141 AC: 21 AN: 149280 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000739

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000539

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000133

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000142 AC: 29 AN: 204072 AF XY: 0.000143

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000727

Gnomad ASJ exome AF: 0.000118

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000481

Gnomad NFE exome AF: 0.0000821

Gnomad OTH exome AF: 0.000422

GnomAD4 exome AF: 0.000147 AC: 208 AN: 1414442 Hom.: 1 Cov.: 30 AF XY: 0.000145 AC XY: 102 AN XY: 703450

African (AFR) AF: 0.0000337 AC: 1 AN: 29702

American (AMR) AF: 0.000635 AC: 21 AN: 33076

Ashkenazi Jewish (ASJ) AF: 0.0000406 AC: 1 AN: 24604

East Asian (EAS) AF: 0.0000273 AC: 1 AN: 36646

South Asian (SAS) AF: 0.00 AC: 0 AN: 79000

European-Finnish (FIN) AF: 0.0000189 AC: 1 AN: 52802

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5630

European-Non Finnish (NFE) AF: 0.000159 AC: 174 AN: 1094660

Other (OTH) AF: 0.000154 AC: 9 AN: 58322

GnomAD4 genome AF: 0.000141 AC: 21 AN: 149346 Hom.: 0 Cov.: 31 AF XY: 0.000124 AC XY: 9 AN XY: 72566

African (AFR) AF: 0.0000737 AC: 3 AN: 40686

American (AMR) AF: 0.000538 AC: 8 AN: 14868

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3452

East Asian (EAS) AF: 0.000196 AC: 1 AN: 5090

South Asian (SAS) AF: 0.00 AC: 0 AN: 4706

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9682

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 276

European-Non Finnish (NFE) AF: 0.000133 AC: 9 AN: 67618

Other (OTH) AF: 0.00 AC: 0 AN: 2066

Alfa AF: 0.000176 Hom.: 0

Bravo AF: 0.000208

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.000108 AC: 13

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	0.084
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.78	T
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.050	T
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.57
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.071
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.16	T
Polyphen		1.0	D
Vest4		0.27
MVP		0.73
MPC		0.15
ClinPred		0.18	T
GERP RS		3.1
Varity_R		0.14
gMVP		0.093
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs550312225; hg19: chr5-133642368; COSMIC: COSV54740443; COSMIC: COSV54740443;