NM_022048.5:c.520C>T

Variant names:

• chr15-64214049-G-A
• rs2140264214
• NM_022048.5:c.520C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_022048.5(CSNK1G1):​c.520C>T​(p.Arg174*) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000205 in 1,461,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. R174R) has been classified as Uncertain significance. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CSNK1G1 NM_022048.5 stop_gained
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.80
• Publications: 0 publications found

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]

CSNK1G1 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000259316 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022048.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSNK1G1	NM_022048.5	MANE Select	c.520C>T	p.Arg174*	stop_gained	Exon 6 of 12	NP_071331.2	Q9HCP0-1
	CSNK1G1	NM_001329605.2		c.520C>T	p.Arg174*	stop_gained	Exon 6 of 13	NP_001316534.1	U3KQB3
	CSNK1G1	NM_001329607.2		c.520C>T	p.Arg174*	stop_gained	Exon 6 of 12	NP_001316536.1	Q8IXA3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSNK1G1	ENST00000303052.13	TSL:1 MANE Select	c.520C>T	p.Arg174*	stop_gained	Exon 6 of 12	ENSP00000305777.7	Q9HCP0-1
	CSNK1G1	ENST00000607537.6	TSL:1	c.520C>T	p.Arg174*	stop_gained	Exon 6 of 13	ENSP00000475724.1	U3KQB3
	CSNK1G1	ENST00000561349.6	TSL:1	c.520C>T	p.Arg174*	stop_gained	Exon 5 of 11	ENSP00000476088.2	Q8IXA3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461824 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727210

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111970

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.65
CADD	Pathogenic	40
DANN	Uncertain	1.0
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.98	D
PhyloP100		5.8
Vest4		0.57
GERP RS		4.9

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

Other links and lift over

dbSNP: rs2140264214; hg19: chr15-64506248; COSMIC: COSV104596325; COSMIC: COSV104596325;