chr15-64259217-T-C

Position:

• chr15-64259217-T-C

Variant summary

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

The NM_022048.5(CSNK1G1):​c.206A>G​(p.Tyr69Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CSNK1G1 NM_022048.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.90

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]

ACMG classification

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	c.206A>G	p.Tyr69Cys	missense_variant	3/12	ENST00000303052.13	NP_071331.2
CSNK1G1	NM_001329605.2	c.206A>G	p.Tyr69Cys	missense_variant	3/13		NP_001316534.1
CSNK1G1	NM_001329607.2	c.206A>G	p.Tyr69Cys	missense_variant	3/12		NP_001316536.1
CSNK1G1	NM_001329606.2	c.206A>G	p.Tyr69Cys	missense_variant	3/12		NP_001316535.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSNK1G1	ENST00000303052.13	c.206A>G	p.Tyr69Cys	missense_variant	3/12	1	NM_022048.5	ENSP00000305777

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 09, 2024

The c.206A>G (p.Y69C) 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 206, causing the tyrosine (Y) at amino acid position 69 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	Pathogenic	0.84
BayesDel_addAF	Uncertain	0.059	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T;T;T;.;T;T;.;.;T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.97	D;D;D;D;.;D;D;D;D
M_CAP	Benign	0.083	D
MetaRNN	Uncertain	0.62	D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.2	M;.;.;.;.;.;.;.;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.91	D
PROVEAN	Pathogenic	-5.5	D;.;.;.;.;.;.;.;.
REVEL	Uncertain	0.31
Sift	Uncertain	0.019	D;.;.;.;.;.;.;.;.
Sift4G	Uncertain	0.012	D;D;D;D;D;D;D;.;.
Polyphen		1.0	D;.;D;.;.;.;.;.;.
Vest4		0.79
MutPred		0.36		Loss of phosphorylation at Y69 (P = 0.0827);Loss of phosphorylation at Y69 (P = 0.0827);Loss of phosphorylation at Y69 (P = 0.0827);Loss of phosphorylation at Y69 (P = 0.0827);Loss of phosphorylation at Y69 (P = 0.0827);Loss of phosphorylation at Y69 (P = 0.0827);Loss of phosphorylation at Y69 (P = 0.0827);Loss of phosphorylation at Y69 (P = 0.0827);Loss of phosphorylation at Y69 (P = 0.0827);
MVP		0.46
MPC		1.5
ClinPred		0.99	D
GERP RS		5.8
Varity_R		0.77
gMVP		0.83

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-64551416;