chrX-18650592-G-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The ENST00000379989.6(CDKL5):c.2980G>T(p.Gly994Trp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000826 in 1,210,071 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G994R) has been classified as Likely benign.
Frequency
Consequence
ENST00000379989.6 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RS1 | NM_000330.4 | c.185-3260C>A | intron_variant | ENST00000379984.4 | |||
CDKL5 | NM_001037343.2 | c.2980G>T | p.Gly994Trp | missense_variant, splice_region_variant | 21/22 | ||
CDKL5 | NM_003159.3 | c.2980G>T | p.Gly994Trp | missense_variant, splice_region_variant | 20/21 | ||
RS1 | XM_047442337.1 | c.-209C>A | 5_prime_UTR_variant | 1/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKL5 | ENST00000379989.6 | c.2980G>T | p.Gly994Trp | missense_variant, splice_region_variant | 21/22 | 1 | |||
CDKL5 | ENST00000379996.7 | c.2980G>T | p.Gly994Trp | missense_variant, splice_region_variant | 20/21 | 1 | |||
RS1 | ENST00000379984.4 | c.185-3260C>A | intron_variant | 1 | NM_000330.4 | P1 | |||
CDKL5 | ENST00000673617.1 | n.252G>T | splice_region_variant, non_coding_transcript_exon_variant | 2/3 |
Frequencies
GnomAD3 genomes AF: 0.00000888 AC: 1AN: 112598Hom.: 0 Cov.: 23 AF XY: 0.0000288 AC XY: 1AN XY: 34732
GnomAD3 exomes AF: 0.00000547 AC: 1AN: 182807Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 67319
GnomAD4 exome AF: 0.00000820 AC: 9AN: 1097473Hom.: 0 Cov.: 30 AF XY: 0.00000827 AC XY: 3AN XY: 362841
GnomAD4 genome AF: 0.00000888 AC: 1AN: 112598Hom.: 0 Cov.: 23 AF XY: 0.0000288 AC XY: 1AN XY: 34732
ClinVar
Not reported inComputational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at