Variant chr22-38294393-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM1BP4_StrongBS2

The NM_152221.3(CSNK1E):c.1027A>G(p.Ser343Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000156 in 1,555,864 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 2 hom. )

Consequence

CSNK1E
NM_152221.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.38

Variant links:

Genes affected

CSNK1E (HGNC:2453): (casein kinase 1 epsilon) The protein encoded by this gene is a serine/threonine protein kinase and a member of the casein kinase I protein family, whose members have been implicated in the control of cytoplasmic and nuclear processes, including DNA replication and repair. The encoded protein is found in the cytoplasm as a monomer and can phosphorylate a variety of proteins, including itself. This protein has been shown to phosphorylate period, a circadian rhythm protein. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Feb 2014]

CSNK1E links:

TPTEP2-CSNK1E (HGNC:):

TPTEP2-CSNK1E links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity KC1E_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.031876683).

BS2

High AC in GnomAd4 at 23 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CSNK1E	NM_152221.3 linkuse as main transcript	c.1027A>G	p.Ser343Gly	missense_variant	8/11	ENST00000396832.6
TPTEP2-CSNK1E	NM_001289912.2 linkuse as main transcript	c.1027A>G	p.Ser343Gly	missense_variant	12/15
CSNK1E	NM_001894.5 linkuse as main transcript	c.1027A>G	p.Ser343Gly	missense_variant	8/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSNK1E	ENST00000396832.6 linkuse as main transcript	c.1027A>G	p.Ser343Gly	missense_variant	8/11	1	NM_152221.3	P1

Frequencies

GnomAD3 genomes

AF:

0.000152

AC:

AN:

151796

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.000578

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000213

AC:

AN:

155136

Hom.:

AF XY:

0.000248

AC XY:

AN XY:

84804

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000391

Gnomad ASJ exome

AF:

0.000485

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000126

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000310

Gnomad OTH exome

AF:

0.00137

GnomAD4 exome

AF:

0.000157

AC:

220

AN:

1403942

Hom.:

Cov.:

AF XY:

0.000163

AC XY:

113

AN XY:

693818

show subpopulations

Gnomad4 AFR exome

AF:

0.000280

Gnomad4 AMR exome

AF:

0.000136

Gnomad4 ASJ exome

AF:

0.000596

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000621

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000126

Gnomad4 OTH exome

AF:

0.000274

GnomAD4 genome

AF:

0.000151

AC:

AN:

151922

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.000578

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000406

Hom.:

Bravo

AF:

0.000291

ExAC

AF:

0.000148

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 14, 2023

The c.1027A>G (p.S343G) alteration is located in exon 8 (coding exon 7) of the CSNK1E gene. This alteration results from a A to G substitution at nucleotide position 1027, causing the serine (S) at amino acid position 343 to be replaced by a glycine (G). 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

Benign

0.055

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.35

DEOGEN2

Benign

0.19

T;T;T;.

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.25

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.65

.;T;.;.

M_CAP

Benign

0.0066

MetaRNN

Benign

0.032

T;T;T;T

MetaSVM

Benign

-0.98

MutationTaster

Benign

0.90

N;N;N;N;N

PrimateAI

Uncertain

0.57

PROVEAN

Benign

0.52

N;N;N;N

REVEL

Benign

0.064

Sift

Benign

0.96

T;T;T;T

Sift4G

Benign

0.56

T;T;T;T

Polyphen

0.0

B;B;B;.

Vest4

0.23

MVP

0.24

MPC

0.47

ClinPred

0.030

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.19

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over