Variant chr22-38294347-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_152221.3(CSNK1E):c.1073C>T(p.Pro358Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000135 in 1,560,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

CSNK1E
NM_152221.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.21

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.

BP4

Computational evidence support a benign effect (MetaRNN=0.07541984).

BS2

High AC in GnomAd4 at 15 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CSNK1E	NM_152221.3 linkuse as main transcript	c.1073C>T	p.Pro358Leu	missense_variant	8/11	ENST00000396832.6
TPTEP2-CSNK1E	NM_001289912.2 linkuse as main transcript	c.1073C>T	p.Pro358Leu	missense_variant	12/15
CSNK1E	NM_001894.5 linkuse as main transcript	c.1073C>T	p.Pro358Leu	missense_variant	8/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSNK1E	ENST00000396832.6 linkuse as main transcript	c.1073C>T	p.Pro358Leu	missense_variant	8/11	1	NM_152221.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0000996

AC:

AN:

150672

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000982

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000192

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000131

AC:

AN:

183002

Hom.:

AF XY:

0.000139

AC XY:

AN XY:

100360

show subpopulations

Gnomad AFR exome

AF:

0.0000994

Gnomad AMR exome

AF:

0.000108

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000240

Gnomad OTH exome

AF:

0.000211

GnomAD4 exome

AF:

0.000139

AC:

196

AN:

1409506

Hom.:

Cov.:

AF XY:

0.000136

AC XY:

AN XY:

697830

show subpopulations

Gnomad4 AFR exome

AF:

0.0000612

Gnomad4 AMR exome

AF:

0.0000772

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000365

Gnomad4 FIN exome

AF:

0.0000244

Gnomad4 NFE exome

AF:

0.000165

Gnomad4 OTH exome

AF:

0.000120

GnomAD4 genome

AF:

0.0000995

AC:

AN:

150800

Hom.:

Cov.:

AF XY:

0.000122

AC XY:

AN XY:

73674

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000982

Gnomad4 NFE

AF:

0.000192

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000352

Hom.:

Bravo

AF:

0.000121

ExAC

AF:

0.0000924

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 17, 2022

The c.1073C>T (p.P358L) alteration is located in exon 8 (coding exon 7) of the CSNK1E gene. This alteration results from a C to T substitution at nucleotide position 1073, causing the proline (P) at amino acid position 358 to be replaced by a leucine (L). 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

0.094

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.69

DEOGEN2

Benign

0.40

T;T;T;.

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.086

FATHMM_MKL

Benign

0.73

LIST_S2

Uncertain

0.89

.;D;.;.

M_CAP

Benign

0.022

MetaRNN

Benign

0.075

T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.97

D;D;D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.80

N;N;N;N

REVEL

Benign

0.059

Sift

Benign

0.36

T;T;T;T

Sift4G

Benign

0.16

T;T;T;T

Polyphen

0.044

B;B;B;.

Vest4

0.18

MVP

0.44

MPC

0.53

ClinPred

0.076

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.062

gMVP

0.11

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