15-64259223-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_022048.5(CSNK1G1):ā€‹c.200A>Gā€‹(p.Asn67Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000106 in 1,597,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 31)
Exomes š‘“: 0.000011 ( 0 hom. )

Consequence

CSNK1G1
NM_022048.5 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.90
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.34440944).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CSNK1G1NM_022048.5 linkuse as main transcriptc.200A>G p.Asn67Ser missense_variant 3/12 ENST00000303052.13 NP_071331.2 Q9HCP0-1A0A024R5W3
CSNK1G1NM_001329605.2 linkuse as main transcriptc.200A>G p.Asn67Ser missense_variant 3/13 NP_001316534.1 U3KQB3
CSNK1G1NM_001329607.2 linkuse as main transcriptc.200A>G p.Asn67Ser missense_variant 3/12 NP_001316536.1 Q8IXA3
CSNK1G1NM_001329606.2 linkuse as main transcriptc.200A>G p.Asn67Ser missense_variant 3/12 NP_001316535.1 Q9HCP0-1A0A024R5W3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CSNK1G1ENST00000303052.13 linkuse as main transcriptc.200A>G p.Asn67Ser missense_variant 3/121 NM_022048.5 ENSP00000305777.7 Q9HCP0-1
ENSG00000259316ENST00000634318.1 linkuse as main transcriptn.*363A>G non_coding_transcript_exon_variant 5/85 ENSP00000489069.1 A0A0U1RQM0
ENSG00000259316ENST00000634318.1 linkuse as main transcriptn.*363A>G 3_prime_UTR_variant 5/85 ENSP00000489069.1 A0A0U1RQM0

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152134
Hom.:
0
Cov.:
31
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:
0.0000129
AC:
3
AN:
232130
Hom.:
0
AF XY:
0.00000798
AC XY:
1
AN XY:
125302
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:
0.0000363
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000958
Gnomad OTH exome
AF:
0.000176
GnomAD4 exome
AF:
0.0000111
AC:
16
AN:
1445822
Hom.:
0
Cov.:
27
AF XY:
0.0000111
AC XY:
8
AN XY:
718644
show subpopulations
Gnomad4 AFR exome
AF:
0.0000303
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000120
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000118
Gnomad4 OTH exome
AF:
0.0000167
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152134
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
74320
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:
0.00000378

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 submitterclinical testingAmbry GeneticsJan 09, 2024The c.200A>G (p.N67S) alteration is located in exon 3 (coding exon 2) of the CSNK1G1 gene. This alteration results from a A to G substitution at nucleotide position 200, causing the asparagine (N) at amino acid position 67 to be replaced by a serine (S). 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
Benign
0.15
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.56
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.16
T;T;T;.;T;T;.;.;T
Eigen
Uncertain
0.37
Eigen_PC
Uncertain
0.47
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.97
D;D;D;D;.;D;D;D;D
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.34
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.8
L;.;.;.;.;.;.;.;.
PrimateAI
Pathogenic
0.80
T
PROVEAN
Uncertain
-4.2
D;.;.;.;.;.;.;.;.
REVEL
Benign
0.17
Sift
Benign
0.090
T;.;.;.;.;.;.;.;.
Sift4G
Benign
0.094
T;T;T;T;T;T;T;.;.
Polyphen
0.37
B;.;P;.;.;.;.;.;.
Vest4
0.51
MutPred
0.37
Gain of relative solvent accessibility (P = 0.1684);Gain of relative solvent accessibility (P = 0.1684);Gain of relative solvent accessibility (P = 0.1684);Gain of relative solvent accessibility (P = 0.1684);Gain of relative solvent accessibility (P = 0.1684);Gain of relative solvent accessibility (P = 0.1684);Gain of relative solvent accessibility (P = 0.1684);Gain of relative solvent accessibility (P = 0.1684);Gain of relative solvent accessibility (P = 0.1684);
MVP
0.48
MPC
0.45
ClinPred
0.55
D
GERP RS
5.8
Varity_R
0.64
gMVP
0.36

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.

Other links and lift over

dbSNP: rs1341995555; hg19: chr15-64551422; COSMIC: COSV57314679; API