14-50345042-C-G

Variant names:

• chr14-50345042-C-G
• rs764133695
• NM_004196.7:c.307G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004196.7(CDKL1):​c.307G>C​(p.Val103Leu) variant causes a missense 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. 12/19 in silico tools predict a benign outcome for this variant. 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. V103M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDKL1 NM_004196.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.92
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21535441).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004196.7. 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
	CDKL1	NM_004196.7	MANE Select	c.307G>C	p.Val103Leu	missense	Exon 4 of 10	NP_004187.3
	CDKL1	NM_001423761.1		c.307G>C	p.Val103Leu	missense	Exon 3 of 9	NP_001410690.1	Q00532-1
	CDKL1	NM_001423762.1		c.307G>C	p.Val103Leu	missense	Exon 4 of 10	NP_001410691.1	A0A9S7JKS7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKL1	ENST00000395834.6	TSL:1 MANE Select	c.307G>C	p.Val103Leu	missense	Exon 4 of 10	ENSP00000379176.2	A0A9S7JKS7
	CDKL1	ENST00000216378.2	TSL:1	c.310G>C	p.Val104Leu	missense	Exon 4 of 9	ENSP00000216378.2	A0A5H1ZRP5
	CDKL1	ENST00000356146.5	TSL:1	n.2227-1984G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	20
DANN	Uncertain	0.99
Eigen	Benign	-0.20
Eigen_PC	Benign	0.0085
FATHMM_MKL	Uncertain	0.87	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.96	T
PhyloP100		2.9
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.25
Sift	Benign	0.48	T
Sift4G	Benign	0.43	T
Vest4		0.34
MVP		0.16
MPC		0.25
ClinPred		0.52	D
GERP RS		4.6
gMVP		0.69
Mutation Taster		=33/67	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs764133695; hg19: chr14-50811760;