Variant 15-64216692-T-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.314A>G(p.Tyr105Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000039 in 1,613,914 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

CSNK1G1
NM_022048.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.30

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.314A>G	p.Tyr105Cys	missense_variant	5/12	ENST00000303052.13	NP_071331.2	Q9HCP0-1A0A024R5W3
CSNK1G1	NM_001329605.2 link	c.314A>G	p.Tyr105Cys	missense_variant	5/13		NP_001316534.1	U3KQB3
CSNK1G1	NM_001329607.2 link	c.314A>G	p.Tyr105Cys	missense_variant	5/12		NP_001316536.1	Q8IXA3
CSNK1G1	NM_001329606.2 link	c.314A>G	p.Tyr105Cys	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.314A>G	p.Tyr105Cys	missense_variant	5/12	1	NM_022048.5	ENSP00000305777.7	Q9HCP0-1
ENSG00000259316	ENST00000634318.1 link	n.*477A>G		non_coding_transcript_exon_variant	7/8	5		ENSP00000489069.1	A0A0U1RQM0
ENSG00000259316	ENST00000634318.1 link	n.*477A>G		3_prime_UTR_variant	7/8	5		ENSP00000489069.1	A0A0U1RQM0

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000517

AC:

AN:

251214

Hom.:

AF XY:

0.0000663

AC XY:

AN XY:

135766

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:

0.000106

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000397

AC:

AN:

1461770

Hom.:

Cov.:

AF XY:

0.0000481

AC XY:

AN XY:

727178

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:

0.0000468

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152144

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

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

Jul 26, 2022

The c.314A>G (p.Y105C) alteration is located in exon 5 (coding exon 4) of the CSNK1G1 gene. This alteration results from a A to G substitution at nucleotide position 314, causing the tyrosine (Y) at amino acid position 105 to be replaced by a cysteine (C). 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

Uncertain

0.42

BayesDel_addAF

Benign

-0.026

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

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

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.82

LIST_S2

Pathogenic

0.99

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

M_CAP

Benign

0.025

MetaRNN

Uncertain

0.44

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

MetaSVM

Benign

-0.91

MutationAssessor

Pathogenic

3.3

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

PrimateAI

Uncertain

0.79

PROVEAN

Pathogenic

-6.9

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

REVEL

Benign

0.28

Sift

Uncertain

0.0010

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

Sift4G

Uncertain

0.040

D;D;D;D;D;D;T;.;.

Polyphen

1.0

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

Vest4

0.68

MVP

0.57

MPC

0.62

ClinPred

0.48

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.90

gMVP

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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