Variant 15-64204948-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The ENST00000303052.13(CSNK1G1):c.767C>G(p.Ala256Gly) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000703 in 1,422,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

CSNK1G1
ENST00000303052.13 missense, splice_region

Scores

Splicing: ADA: 0.9910

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.95

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.835

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CSNK1G1	NM_022048.5 linkuse as main transcript	c.767C>G	p.Ala256Gly	missense_variant, splice_region_variant	8/12	ENST00000303052.13	NP_071331.2
CSNK1G1	NM_001329605.2 linkuse as main transcript	c.767C>G	p.Ala256Gly	missense_variant, splice_region_variant	8/13		NP_001316534.1
CSNK1G1	NM_001329607.2 linkuse as main transcript	c.767C>G	p.Ala256Gly	missense_variant, splice_region_variant	8/12		NP_001316536.1
CSNK1G1	NM_001329606.2 linkuse as main transcript	c.767C>G	p.Ala256Gly	missense_variant, splice_region_variant	8/12		NP_001316535.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSNK1G1	ENST00000303052.13 linkuse as main transcript	c.767C>G	p.Ala256Gly	missense_variant, splice_region_variant	8/12	1	NM_022048.5	ENSP00000305777		Q9HCP0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.03e-7

AC:

AN:

1422644

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

709788

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.28e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 07, 2024

The c.767C>G (p.A256G) alteration is located in exon 8 (coding exon 7) of the CSNK1G1 gene. This alteration results from a C to G substitution at nucleotide position 767, causing the alanine (A) at amino acid position 256 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Uncertain

0.069

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

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

Eigen

Pathogenic

0.90

Eigen_PC

Pathogenic

0.91

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Pathogenic

0.98

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

M_CAP

Benign

0.081

MetaRNN

Pathogenic

0.84

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

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.87

PROVEAN

Uncertain

-3.8

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

REVEL

Uncertain

0.46

Sift

Uncertain

0.0010

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

Sift4G

Uncertain

0.011

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

Polyphen

1.0

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

Vest4

0.71

MutPred

0.73

Gain of disorder (P = 0.0876);Gain of disorder (P = 0.0876);Gain of disorder (P = 0.0876);Gain of disorder (P = 0.0876);Gain of disorder (P = 0.0876);Gain of disorder (P = 0.0876);Gain of disorder (P = 0.0876);

MVP

0.53

MPC

0.71

ClinPred

0.98

GERP RS

6.2

Varity_R

0.85

gMVP

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Pathogenic

0.83

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

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