dbSNP rs759763094: CSNK1G1:p.Arg291Leu (chr15-64204568-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_022048.5(CSNK1G1):c.872G>T(p.Arg291Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,534 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R291Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CSNK1G1
NM_022048.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.91

Variant links:

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 links:

ENSG00000259316 (HGNC:):

ENSG00000259316 links:

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ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
CSNK1G1	NM_022048.5 link	c.872G>T	p.Arg291Leu	missense_variant	Exon 9 of 12	ENST00000303052.13	NP_071331.2	Q9HCP0-1A0A024R5W3
CSNK1G1	NM_001329605.2 link	c.872G>T	p.Arg291Leu	missense_variant	Exon 9 of 13		NP_001316534.1	U3KQB3
CSNK1G1	NM_001329607.2 link	c.872G>T	p.Arg291Leu	missense_variant	Exon 9 of 12		NP_001316536.1	Q8IXA3
CSNK1G1	NM_001329606.2 link	c.872G>T	p.Arg291Leu	missense_variant	Exon 9 of 12		NP_001316535.1	Q9HCP0-1A0A024R5W3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSNK1G1	ENST00000303052.13 link	c.872G>T	p.Arg291Leu	missense_variant	Exon 9 of 12	1	NM_022048.5	ENSP00000305777.7		Q9HCP0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461534

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727080

show subpopulations

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.70

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.070

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

T;T;T;.;T;T;T;T;.

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.88

D;D;D;D;.;D;D;D;D

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.69

D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.2

L;.;.;.;.;.;.;.;.

PrimateAI

Pathogenic

0.89

PROVEAN

Pathogenic

-6.6

D;.;.;.;.;.;.;.;.

REVEL

Uncertain

0.38

Sift

Uncertain

0.0090

D;.;.;.;.;.;.;.;.

Sift4G

Benign

0.15

T;T;T;T;T;T;D;D;T

Polyphen

0.15

B;.;B;.;.;.;.;.;.

Vest4

0.91

MutPred

0.41

Loss of phosphorylation at T288 (P = 0.2176);Loss of phosphorylation at T288 (P = 0.2176);Loss of phosphorylation at T288 (P = 0.2176);Loss of phosphorylation at T288 (P = 0.2176);Loss of phosphorylation at T288 (P = 0.2176);Loss of phosphorylation at T288 (P = 0.2176);.;.;Loss of phosphorylation at T288 (P = 0.2176);

MVP

0.80

MPC

0.81

ClinPred

0.98

GERP RS

5.7

Varity_R

0.69

gMVP

0.86

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over