15-64204443-T-C

Variant names:

• chr15-64204443-T-C
• NM_022048.5:c.997A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022048.5(CSNK1G1):​c.997A>G​(p.Ile333Val) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CSNK1G1 NM_022048.5 missense, splice_region
• Scores: Splicing: ADA: 0.1905
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.11

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]

ENSG00000259316 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24828818).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSNK1G1	NM_022048.5	c.997A>G	p.Ile333Val	missense_variant, splice_region_variant	Exon 9 of 12	ENST00000303052.13	NP_071331.2
CSNK1G1	NM_001329605.2	c.997A>G	p.Ile333Val	missense_variant, splice_region_variant	Exon 9 of 13		NP_001316534.1
CSNK1G1	NM_001329607.2	c.997A>G	p.Ile333Val	missense_variant, splice_region_variant	Exon 9 of 12		NP_001316536.1
CSNK1G1	NM_001329606.2	c.997A>G	p.Ile333Val	missense_variant, splice_region_variant	Exon 9 of 12		NP_001316535.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSNK1G1	ENST00000303052.13	c.997A>G	p.Ile333Val	missense_variant, splice_region_variant	Exon 9 of 12	1	NM_022048.5	ENSP00000305777.7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CSNK1G1: PM2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Uncertain	0.024	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.027	T;T;T;.;T;T;T;T;T;.;T
Eigen	Benign	0.056
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.93	D;D;D;D;.;D;D;D;D;D;D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.25	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.76	T
MutationAssessor	Uncertain	2.4	M;.;.;.;.;.;.;.;.;.;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.37	N;.;.;.;.;.;.;.;.;.;.
REVEL	Benign	0.10
Sift	Benign	0.15	T;.;.;.;.;.;.;.;.;.;.
Sift4G	Benign	0.42	T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.0010	B;.;B;.;.;.;.;.;.;.;.
Vest4		0.38
MutPred		0.33		Gain of disorder (P = 0.1078);Gain of disorder (P = 0.1078);Gain of disorder (P = 0.1078);Gain of disorder (P = 0.1078);Gain of disorder (P = 0.1078);Gain of disorder (P = 0.1078);.;.;.;Gain of disorder (P = 0.1078);.;
MVP		0.69
MPC		0.42
ClinPred		0.72	D
GERP RS		5.7
Varity_R		0.17
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.19
dbscSNV1_RF	Benign	0.32
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-64496642;