15-64203144-T-G

Variant names:

• chr15-64203144-T-G
• rs372653620
• NM_022048.5:c.1045A>C

Variant summary

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

The NM_022048.5(CSNK1G1):​c.1045A>C​(p.Ile349Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I349V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CSNK1G1 NM_022048.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.437

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=0.09297562).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSNK1G1	NM_022048.5	c.1045A>C	p.Ile349Leu	missense_variant	Exon 10 of 12	ENST00000303052.13	NP_071331.2
CSNK1G1	NM_001329605.2	c.1045A>C	p.Ile349Leu	missense_variant	Exon 10 of 13		NP_001316534.1
CSNK1G1	NM_001329607.2	c.1045A>C	p.Ile349Leu	missense_variant	Exon 10 of 12		NP_001316536.1
CSNK1G1	NM_001329606.2	c.1045A>C	p.Ile349Leu	missense_variant	Exon 10 of 12		NP_001316535.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSNK1G1	ENST00000303052.13	c.1045A>C	p.Ile349Leu	missense_variant	Exon 10 of 12	1	NM_022048.5	ENSP00000305777.7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	20
DANN	Benign	0.95
DEOGEN2	Benign	0.028	T;T;T;.;T;T;T;T;T;.;T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.27
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.90	D;T;D;D;.;T;D;D;D;T;D
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.093	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.4	L;.;.;.;.;.;.;.;.;.;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.63	N;.;.;.;.;.;.;.;.;.;.
REVEL	Benign	0.11
Sift	Benign	0.44	T;.;.;.;.;.;.;.;.;.;.
Sift4G	Benign	0.77	T;T;T;T;T;T;T;T;T;T;D
Polyphen		0.0	B;.;B;.;.;.;.;.;.;.;.
Vest4		0.32
MutPred		0.12		Loss of glycosylation at T350 (P = 0.1346);Loss of glycosylation at T350 (P = 0.1346);Loss of glycosylation at T350 (P = 0.1346);Loss of glycosylation at T350 (P = 0.1346);Loss of glycosylation at T350 (P = 0.1346);Loss of glycosylation at T350 (P = 0.1346);.;.;.;Loss of glycosylation at T350 (P = 0.1346);.;
MVP		0.23
MPC		0.47
ClinPred		0.29	T
GERP RS		2.8
Varity_R		0.11
gMVP		0.42

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

Other links and lift over

dbSNP: rs372653620; hg19: chr15-64495343;