X-18425593-C-T

Variant names:

• chrX-18425593-C-T
• rs587783397
• ENST00000379996:c.-265C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000379996(CDKL5):​c.-265C>T variant causes a 5 prime UTR 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 25)
• Consequence: CDKL5 ENST00000379996 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.339

Genes affected

CDKL5 (HGNC:11411): (cyclin dependent kinase like 5) This gene is a member of Ser/Thr protein kinase family and encodes a phosphorylated protein with protein kinase activity. Mutations in this gene have been associated with X-linked infantile spasm syndrome (ISSX), also known as X-linked West syndrome, and Rett syndrome (RTT). Alternate transcriptional splice variants have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKL5	NM_001323289.2	c.-265C>T		upstream_gene_variant		ENST00000623535.2	NP_001310218.1
CDKL5	NM_003159.3	c.-265C>T		upstream_gene_variant			NP_003150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKL5	ENST00000379996	c.-265C>T		5_prime_UTR_variant	Exon 1 of 21	1		ENSP00000369332.3
CDKL5	ENST00000623535.2	c.-265C>T		upstream_gene_variant		1	NM_001323289.2	ENSP00000485244.1
CDKL5	ENST00000674046.1	c.-265C>T		upstream_gene_variant				ENSP00000501174.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	15
DANN	Uncertain	0.98

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs587783397; hg19: chrX-18443713;