rs368793081

Variant summary

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

The NM_004196.7(CDKL1):​c.226C>T​(p.Leu76Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,612,946 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 30)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CDKL1
NM_004196.7 missense

Scores

1
9
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.58
Variant links:
Genes affected
CDKL1 (HGNC:1781): (cyclin dependent kinase like 1) This gene product is a member of a large family of CDC2-related serine/threonine protein kinases that accumulates primarily in the nucleus. [provided by RefSeq, Nov 2018]

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=0.40374938).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CDKL1NM_004196.7 linkc.226C>T p.Leu76Phe missense_variant Exon 3 of 10 ENST00000395834.6 NP_004187.3 Q00532

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CDKL1ENST00000395834.6 linkc.226C>T p.Leu76Phe missense_variant Exon 3 of 10 1 NM_004196.7 ENSP00000379176.2

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152142
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.000145
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1460804
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
2
AN XY:
726754
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152142
Hom.:
0
Cov.:
30
AF XY:
0.0000404
AC XY:
3
AN XY:
74338
show subpopulations
Gnomad4 AFR
AF:
0.000145
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:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.0000378
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.41
BayesDel_addAF
Pathogenic
0.20
D
BayesDel_noAF
Uncertain
0.050
CADD
Uncertain
25
DANN
Uncertain
1.0
Eigen
Uncertain
0.52
Eigen_PC
Uncertain
0.56
FATHMM_MKL
Uncertain
0.93
D
M_CAP
Benign
0.026
D
MetaRNN
Benign
0.40
T;T
MetaSVM
Benign
-0.31
T
PrimateAI
Uncertain
0.65
T
PROVEAN
Uncertain
-3.6
D;D
REVEL
Uncertain
0.53
Sift
Benign
0.084
T;T
Sift4G
Benign
0.094
T;D
Vest4
0.56
MVP
0.46
MPC
0.57
ClinPred
0.98
D
GERP RS
5.0
gMVP
0.46

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.

Other links and lift over

dbSNP: rs368793081; hg19: chr14-50825810; API