15-64171950-G-C

Variant names:

• chr15-64171950-G-C
• rs763267924
• NM_022048.5:c.1250C>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.1250C>G​(p.Thr417Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000212 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: CSNK1G1 NM_022048.5 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.087302655).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSNK1G1	NM_022048.5	c.1250C>G	p.Thr417Ser	missense_variant	Exon 12 of 12	ENST00000303052.13	NP_071331.2
CSNK1G1	NM_001329606.2	c.1250C>G	p.Thr417Ser	missense_variant	Exon 12 of 12		NP_001316535.1
CSNK1G1	NM_001329605.2	c.1326-5870C>G		intron_variant	Intron 12 of 12		NP_001316534.1
CSNK1G1	NM_001329607.2	c.1215-5870C>G		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>G	p.Thr417Ser	missense_variant	Exon 12 of 12	1	NM_022048.5	ENSP00000305777.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000401 AC: 1 AN: 249500 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135372

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: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000212 AC: 31 AN: 1461842 Hom.: 0 Cov.: 30 AF XY: 0.0000193 AC XY: 14 AN XY: 727222

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000279

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	19
DANN	Benign	0.89
DEOGEN2	Benign	0.018	T;.;T;T;T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.86	D;D;.;D;D
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.087	T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.090	N;.;.;.;.
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.010	N;.;.;.;.
REVEL	Benign	0.11
Sift	Benign	0.67	T;.;.;.;.
Sift4G	Benign	0.87	T;T;T;T;T
Polyphen		0.0	B;.;.;.;.
Vest4		0.094
MutPred		0.24		Gain of sheet (P = 0.1208);.;.;.;.;
MVP		0.40
MPC		0.42
ClinPred		0.14	T
GERP RS		4.7
Varity_R		0.068

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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;