Variant 15-64216663-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.343G>A(p.Ala115Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,692 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CSNK1G1
NM_022048.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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:

ENSG00000259316 (HGNC:):

ENSG00000259316 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	UniProt
CSNK1G1	NM_022048.5 link	c.343G>A	p.Ala115Thr	missense_variant	5/12	ENST00000303052.13	NP_071331.2	Q9HCP0-1A0A024R5W3
CSNK1G1	NM_001329605.2 link	c.343G>A	p.Ala115Thr	missense_variant	5/13		NP_001316534.1	U3KQB3
CSNK1G1	NM_001329607.2 link	c.343G>A	p.Ala115Thr	missense_variant	5/12		NP_001316536.1	Q8IXA3
CSNK1G1	NM_001329606.2 link	c.343G>A	p.Ala115Thr	missense_variant	5/12		NP_001316535.1	Q9HCP0-1A0A024R5W3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CSNK1G1	ENST00000303052.13 link	c.343G>A	p.Ala115Thr	missense_variant	5/12	1	NM_022048.5	ENSP00000305777.7	Q9HCP0-1
ENSG00000259316	ENST00000634318.1 link	n.*506G>A		non_coding_transcript_exon_variant	7/8	5		ENSP00000489069.1	A0A0U1RQM0
ENSG00000259316	ENST00000634318.1 link	n.*506G>A		3_prime_UTR_variant	7/8	5		ENSP00000489069.1	A0A0U1RQM0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251140

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135730

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461692

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727152

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

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

Aug 06, 2024

The c.343G>A (p.A115T) alteration is located in exon 5 (coding exon 4) of the CSNK1G1 gene. This alteration results from a G to A substitution at nucleotide position 343, causing the alanine (A) at amino acid position 115 to be replaced by a threonine (T). 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

0.98

BayesDel_addAF

Benign

-0.030

BayesDel_noAF

Benign

-0.28

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.16

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

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.87

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

M_CAP

Benign

0.030

MetaRNN

Uncertain

0.54

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

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.1

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

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-3.4

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

REVEL

Uncertain

0.34

Sift

Uncertain

0.0070

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

Sift4G

Uncertain

0.014

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

Polyphen

1.0

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

Vest4

0.77

MutPred

0.51

Gain of phosphorylation at A115 (P = 0.1151);Gain of phosphorylation at A115 (P = 0.1151);Gain of phosphorylation at A115 (P = 0.1151);Gain of phosphorylation at A115 (P = 0.1151);Gain of phosphorylation at A115 (P = 0.1151);Gain of phosphorylation at A115 (P = 0.1151);Gain of phosphorylation at A115 (P = 0.1151);Gain of phosphorylation at A115 (P = 0.1151);Gain of phosphorylation at A115 (P = 0.1151);

MVP

0.54

MPC

1.2

ClinPred

0.96

GERP RS

4.6

Varity_R

0.86

gMVP

0.81

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