15-64216564-G-C

Position:

• chr15-64216564-G-C

Variant summary

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

The NM_022048.5(CSNK1G1):​c.442C>G​(p.Leu148Val) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000684 in 1,461,360 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CSNK1G1 NM_022048.5 missense, splice_region
• Scores: Splicing: ADA: 0.00004876
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.98

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSNK1G1	NM_022048.5	c.442C>G	p.Leu148Val	missense_variant, splice_region_variant	5/12	ENST00000303052.13	NP_071331.2
CSNK1G1	NM_001329605.2	c.442C>G	p.Leu148Val	missense_variant, splice_region_variant	5/13		NP_001316534.1
CSNK1G1	NM_001329607.2	c.442C>G	p.Leu148Val	missense_variant, splice_region_variant	5/12		NP_001316536.1
CSNK1G1	NM_001329606.2	c.442C>G	p.Leu148Val	missense_variant, splice_region_variant	5/12		NP_001316535.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSNK1G1	ENST00000303052.13	c.442C>G	p.Leu148Val	missense_variant, splice_region_variant	5/12	1	NM_022048.5	ENSP00000305777.7
ENSG00000259316	ENST00000634318.1	n.*605C>G		splice_region_variant, non_coding_transcript_exon_variant	7/8	5		ENSP00000489069.1
ENSG00000259316	ENST00000634318.1	n.*605C>G		3_prime_UTR_variant	7/8	5		ENSP00000489069.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 249966 Hom.: 0 AF XY: 0.00000739 AC XY: 1 AN XY: 135236

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461360 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726998

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T;T;T;.;T;T;.;.
Eigen	Benign	0.14
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.96	D;D;D;D;.;D;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.72	D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.33	T
MutationAssessor	Uncertain	2.3	M;.;.;.;.;.;.;.
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-2.4	N;.;.;.;.;.;.;.
REVEL	Uncertain	0.40
Sift	Uncertain	0.0010	D;.;.;.;.;.;.;.
Sift4G	Uncertain	0.0030	D;D;D;D;D;D;D;.
Polyphen		0.90	P;.;P;.;.;.;.;.
Vest4		0.66
MutPred		0.57		Gain of catalytic residue at L148 (P = 0.0107);Gain of catalytic residue at L148 (P = 0.0107);Gain of catalytic residue at L148 (P = 0.0107);Gain of catalytic residue at L148 (P = 0.0107);Gain of catalytic residue at L148 (P = 0.0107);Gain of catalytic residue at L148 (P = 0.0107);Gain of catalytic residue at L148 (P = 0.0107);Gain of catalytic residue at L148 (P = 0.0107);
MVP		0.79
MPC		1.3
ClinPred		0.92	D
GERP RS		4.0
Varity_R		0.85
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000049
dbscSNV1_RF	Benign	0.078
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: rs6494466; hg19: chr15-64508763;