Variant 15-64216564-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_022048.5(CSNK1G1):c.442C>G(p.Leu148Val) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000684 in 1,461,360 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CSNK1G1
NM_022048.5 missense, splice_region

Scores

Splicing: ADA: 0.00004876

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.98

Variant links:

Genes affected

CSNK1G1 (HGNC:2454): (casein kinase 1 gamma 1) This gene encodes a member of the casein kinase I gene family. This family is comprised of serine/threonine kinases that phosphorylate acidic proteins such as caseins. The encoded kinase plays a role in cell cycle checkpoint arrest in response to stalled replication forks by phosphorylating Claspin. A mutation in this gene may be associated with non-syndromic early-onset epilepsy (NSEOE). [provided by RefSeq, Jul 2016]

CSNK1G1 links:

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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/exons	MANE
CSNK1G1	NM_022048.5 linkuse as main transcript	c.442C>G	p.Leu148Val	missense_variant, splice_region_variant	5/12	ENST00000303052.13
CSNK1G1	NM_001329605.2 linkuse as main transcript	c.442C>G	p.Leu148Val	missense_variant, splice_region_variant	5/13
CSNK1G1	NM_001329607.2 linkuse as main transcript	c.442C>G	p.Leu148Val	missense_variant, splice_region_variant	5/12
CSNK1G1	NM_001329606.2 linkuse as main transcript	c.442C>G	p.Leu148Val	missense_variant, splice_region_variant	5/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSNK1G1	ENST00000303052.13 linkuse as main transcript	c.442C>G	p.Leu148Val	missense_variant, splice_region_variant	5/12	1	NM_022048.5		Q9HCP0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

249966

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135236

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

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:

6.84e-7

AC:

AN:

1461360

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726998

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Uncertain

0.032

BayesDel_noAF

Uncertain

-0.020

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

T;T;T;.;T;T;.;.

Eigen

Benign

0.14

Eigen_PC

Benign

0.13

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.96

D;D;D;D;.;D;D;D

M_CAP

Uncertain

0.11

MetaRNN

Uncertain

0.72

D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.33

MutationAssessor

Uncertain

2.3

M;.;.;.;.;.;.;.

MutationTaster

Benign

3.5e-9

P;P

PrimateAI

Pathogenic

0.87

PROVEAN

Uncertain

-2.4

N;.;.;.;.;.;.;.

REVEL

Uncertain

0.40

Sift

Uncertain

0.0010

D;.;.;.;.;.;.;.

Sift4G

Uncertain

0.0030

D;D;D;D;D;D;D;.

Polyphen

0.90

P;.;P;.;.;.;.;.

Vest4

0.66

MutPred

0.57

Gain of catalytic residue at L148 (P = 0.0107);Gain of catalytic residue at L148 (P = 0.0107);Gain of catalytic residue at L148 (P = 0.0107);Gain of catalytic residue at L148 (P = 0.0107);Gain of catalytic residue at L148 (P = 0.0107);Gain of catalytic residue at L148 (P = 0.0107);Gain of catalytic residue at L148 (P = 0.0107);Gain of catalytic residue at L148 (P = 0.0107);

MVP

0.79

MPC

1.3

ClinPred

0.92

GERP RS

4.0

Varity_R

0.85

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000049

dbscSNV1_RF

Benign

0.078

SpliceAI score (max)

0.12

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over