chr15-64214048-C-G

Position:

• chr15-64214048-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_022048.5(CSNK1G1):​c.521G>C​(p.Arg174Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 7.91

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.849

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSNK1G1	NM_022048.5	c.521G>C	p.Arg174Pro	missense_variant	6/12	ENST00000303052.13	NP_071331.2
CSNK1G1	NM_001329605.2	c.521G>C	p.Arg174Pro	missense_variant	6/13		NP_001316534.1
CSNK1G1	NM_001329607.2	c.521G>C	p.Arg174Pro	missense_variant	6/12		NP_001316536.1
CSNK1G1	NM_001329606.2	c.521G>C	p.Arg174Pro	missense_variant	6/12		NP_001316535.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSNK1G1	ENST00000303052.13	c.521G>C	p.Arg174Pro	missense_variant	6/12	1	NM_022048.5	ENSP00000305777

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Dec 31, 2023

The c.521G>C (p.R174P) alteration is located in exon 6 (coding exon 5) of the CSNK1G1 gene. This alteration results from a G to C substitution at nucleotide position 521, causing the arginine (R) at amino acid position 174 to be replaced by a proline (P). 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	0.98
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T;T;T;.;T;T;.;.
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;D;D;D;.;D;D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.85	D;D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Uncertain	2.1	M;.;.;.;.;.;.;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.89	D
PROVEAN	Pathogenic	-6.1	D;.;.;.;.;.;.;.
REVEL	Uncertain	0.61
Sift	Uncertain	0.011	D;.;.;.;.;.;.;.
Sift4G	Uncertain	0.051	T;D;D;D;D;D;D;.
Polyphen		1.0	D;.;D;.;.;.;.;.
Vest4		0.81
MutPred		0.47		Gain of ubiquitination at K178 (P = 0.0458);Gain of ubiquitination at K178 (P = 0.0458);Gain of ubiquitination at K178 (P = 0.0458);Gain of ubiquitination at K178 (P = 0.0458);Gain of ubiquitination at K178 (P = 0.0458);Gain of ubiquitination at K178 (P = 0.0458);Gain of ubiquitination at K178 (P = 0.0458);Gain of ubiquitination at K178 (P = 0.0458);
MVP		0.73
MPC		1.7
ClinPred		0.99	D
GERP RS		5.8
Varity_R		0.96
gMVP		0.91

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: chr15-64506247;