Variant chr15-64300420-C-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.80G>A(p.Arg27Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,613,988 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

CSNK1G1
NM_022048.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 7.91

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	Protein
CSNK1G1	NM_022048.5 linkuse as main transcript	c.80G>A	p.Arg27Gln	missense_variant	2/12	ENST00000303052.13	NP_071331.2
CSNK1G1	NM_001329605.2 linkuse as main transcript	c.80G>A	p.Arg27Gln	missense_variant	2/13		NP_001316534.1
CSNK1G1	NM_001329607.2 linkuse as main transcript	c.80G>A	p.Arg27Gln	missense_variant	2/12		NP_001316536.1
CSNK1G1	NM_001329606.2 linkuse as main transcript	c.80G>A	p.Arg27Gln	missense_variant	2/12		NP_001316535.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSNK1G1	ENST00000303052.13 linkuse as main transcript	c.80G>A	p.Arg27Gln	missense_variant	2/12	1	NM_022048.5	ENSP00000305777		Q9HCP0-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251486

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

0.00000958

AC:

AN:

1461838

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000989

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152150

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	Ambry Genetics	May 09, 2023	The c.80G>A (p.R27Q) alteration is located in exon 2 (coding exon 1) of the CSNK1G1 gene. This alteration results from a G to A substitution at nucleotide position 80, causing the arginine (R) at amino acid position 27 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Uncertain significance, criteria provided, single submitter	clinical testing	Mendelics	May 04, 2022	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Uncertain

0.045

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.054

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

Eigen

Uncertain

0.63

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

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

M_CAP

Benign

0.085

MetaRNN

Uncertain

0.51

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

MetaSVM

Uncertain

-0.15

MutationAssessor

Uncertain

2.6

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

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-2.3

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

REVEL

Uncertain

0.35

Sift

Benign

0.040

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

Sift4G

Benign

0.12

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

Polyphen

0.92

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

Vest4

0.57

MutPred

0.21

Loss of MoRF binding (P = 0.0222);Loss of MoRF binding (P = 0.0222);Loss of MoRF binding (P = 0.0222);Loss of MoRF binding (P = 0.0222);Loss of MoRF binding (P = 0.0222);Loss of MoRF binding (P = 0.0222);Loss of MoRF binding (P = 0.0222);Loss of MoRF binding (P = 0.0222);Loss of MoRF binding (P = 0.0222);

MVP

0.72

MPC

1.1

ClinPred

0.75

GERP RS

5.7

Varity_R

0.24

gMVP

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over