14-50395759-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004196.7(CDKL1):​c.110A>C​(p.Glu37Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,461,698 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

CDKL1
NM_004196.7 missense

Scores

3
7
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.92
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CDKL1NM_004196.7 linkc.110A>C p.Glu37Ala missense_variant Exon 2 of 10 ENST00000395834.6 NP_004187.3 Q00532

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CDKL1ENST00000395834.6 linkc.110A>C p.Glu37Ala missense_variant Exon 2 of 10 1 NM_004196.7 ENSP00000379176.2
CDKL1ENST00000216378.2 linkc.113A>C p.Glu38Ala missense_variant Exon 2 of 9 1 ENSP00000216378.2 Q00532-3A0A5H1ZRP5
CDKL1ENST00000356146.5 linkn.680A>C non_coding_transcript_exon_variant Exon 5 of 20 1
CDKL1ENST00000531052.1 linkn.318A>C non_coding_transcript_exon_variant Exon 1 of 3 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000318
AC:
8
AN:
251454
Hom.:
0
AF XY:
0.0000368
AC XY:
5
AN XY:
135906
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000794
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000171
AC:
25
AN:
1461698
Hom.:
0
Cov.:
30
AF XY:
0.0000220
AC XY:
16
AN XY:
727186
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.000727
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000508
Hom.:
0
Bravo
AF:
0.0000113
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 19, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.113A>C (p.E38A) alteration is located in exon 1 (coding exon 1) of the CDKL1 gene. This alteration results from a A to C substitution at nucleotide position 113, causing the glutamic acid (E) at amino acid position 38 to be replaced by an alanine (A). 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
Uncertain
0.38
BayesDel_addAF
Pathogenic
0.28
D
BayesDel_noAF
Pathogenic
0.16
CADD
Uncertain
24
DANN
Uncertain
0.99
Eigen
Benign
0.16
Eigen_PC
Benign
0.18
FATHMM_MKL
Uncertain
0.97
D
M_CAP
Benign
0.081
D
MetaRNN
Uncertain
0.55
D;D
MetaSVM
Benign
-0.64
T
PrimateAI
Uncertain
0.62
T
PROVEAN
Pathogenic
-4.8
D;D
REVEL
Uncertain
0.52
Sift
Benign
0.039
D;D
Sift4G
Uncertain
0.043
D;T
Vest4
0.72
MVP
0.72
MPC
0.35
ClinPred
0.57
D
GERP RS
4.3
gMVP
0.53

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: rs373202347; hg19: chr14-50862477; API