Variant chr15-64216564-G-T 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>A(p.Leu148Met) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000186 in 1,613,306 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: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CSNK1G1
NM_022048.5 missense, splice_region

Scores

Splicing: ADA: 0.000006160

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>A	p.Leu148Met	missense_variant, splice_region_variant	5/12	ENST00000303052.13
CSNK1G1	NM_001329605.2 linkuse as main transcript	c.442C>A	p.Leu148Met	missense_variant, splice_region_variant	5/13
CSNK1G1	NM_001329607.2 linkuse as main transcript	c.442C>A	p.Leu148Met	missense_variant, splice_region_variant	5/12
CSNK1G1	NM_001329606.2 linkuse as main transcript	c.442C>A	p.Leu148Met	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>A	p.Leu148Met	missense_variant, splice_region_variant	5/12	1	NM_022048.5		Q9HCP0-1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151946

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000800

AC:

AN:

249966

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135236

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

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:

0.00000137

AC:

AN:

1461360

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726998

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

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

AF:

0.00000658

AC:

AN:

151946

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74216

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.55

BayesDel_addAF

Benign

-0.018

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.082

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

Eigen

Benign

-0.035

Eigen_PC

Benign

-0.0043

FATHMM_MKL

Benign

0.73

LIST_S2

Uncertain

0.94

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

M_CAP

Benign

0.042

MetaRNN

Uncertain

0.49

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.66

MutationAssessor

Benign

-0.41

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

MutationTaster

Benign

4.4e-9

P;P

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-1.7

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

REVEL

Uncertain

0.40

Sift

Benign

0.33

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

Sift4G

Benign

1.0

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

Polyphen

1.0

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

Vest4

0.58

MutPred

0.63

Gain of catalytic residue at L148 (P = 0.1393);Gain of catalytic residue at L148 (P = 0.1393);Gain of catalytic residue at L148 (P = 0.1393);Gain of catalytic residue at L148 (P = 0.1393);Gain of catalytic residue at L148 (P = 0.1393);Gain of catalytic residue at L148 (P = 0.1393);Gain of catalytic residue at L148 (P = 0.1393);Gain of catalytic residue at L148 (P = 0.1393);

MVP

0.82

MPC

1.3

ClinPred

0.50

GERP RS

4.0

Varity_R

0.40

gMVP

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0000062

dbscSNV1_RF

Benign

0.030

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.

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