15-64171950-G-A

Variant names:

• chr15-64171950-G-A
• rs763267924
• NM_022048.5:c.1250C>T

Variant summary

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

The NM_022048.5(CSNK1G1):​c.1250C>T​(p.Thr417Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CSNK1G1 NM_022048.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.63

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2071859).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSNK1G1	NM_022048.5	c.1250C>T	p.Thr417Ile	missense_variant	Exon 12 of 12	ENST00000303052.13	NP_071331.2
CSNK1G1	NM_001329606.2	c.1250C>T	p.Thr417Ile	missense_variant	Exon 12 of 12		NP_001316535.1
CSNK1G1	NM_001329605.2	c.1326-5870C>T		intron_variant	Intron 12 of 12		NP_001316534.1
CSNK1G1	NM_001329607.2	c.1215-5870C>T		intron_variant	Intron 11 of 11		NP_001316536.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSNK1G1	ENST00000303052.13	c.1250C>T	p.Thr417Ile	missense_variant	Exon 12 of 12	1	NM_022048.5	ENSP00000305777.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Jun 22, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 417 of the CSNK1G1 protein (p.Thr417Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CSNK1G1-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.017	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	D;.;T;T;T
Eigen	Benign	-0.0074
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.97	D;D;.;D;D
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.21	T;T;T;T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	0.81	L;.;.;.;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-2.6	D;.;.;.;.
REVEL	Benign	0.12
Sift	Uncertain	0.0060	D;.;.;.;.
Sift4G	Benign	0.11	T;D;D;D;D
Polyphen		0.023	B;.;.;.;.
Vest4		0.27
MutPred		0.26		Loss of phosphorylation at T417 (P = 0.0017);.;.;.;.;
MVP		0.55
MPC		0.53
ClinPred		0.65	D
GERP RS		4.7
Varity_R		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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

Other links and lift over

dbSNP: rs763267924; hg19: chr15-64464149;