chr22-38294393-T-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -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. 13/21 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

Publications

2 publications found

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:53829): (TPTEP2-CSNK1E readthrough) This locus represents naturally occurring readthrough transcription between the neighboring LOC400927 (transmembrane phosphoinositide 3-phosphatase and tensin homolog 2 pseudogene) and CSNK1E (casein kinase I isoform epsilon) genes on chromosome 22. The readthrough transcript encodes the same protein as the downstream gene product (casein kinase I isoform epsilon). [provided by RefSeq, Feb 2014]

TPTEP2-CSNK1E links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152221.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CSNK1E	NM_152221.3	MANE Select	c.1027A>G	p.Ser343Gly	missense	Exon 8 of 11	NP_689407.1	P49674
TPTEP2-CSNK1E	NM_001289912.2		c.1027A>G	p.Ser343Gly	missense	Exon 12 of 15	NP_001276841.1
CSNK1E	NM_001894.5		c.1027A>G	p.Ser343Gly	missense	Exon 8 of 11	NP_001885.1	P49674

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CSNK1E	ENST00000396832.6	TSL:1 MANE Select	c.1027A>G	p.Ser343Gly	missense	Exon 8 of 11	ENSP00000380044.1	P49674
CSNK1E	ENST00000359867.7	TSL:1	c.1027A>G	p.Ser343Gly	missense	Exon 8 of 11	ENSP00000352929.3	P49674
TPTEP2-CSNK1E	ENST00000400206.7	TSL:2	c.1027A>G	p.Ser343Gly	missense	Exon 12 of 15	ENSP00000383067.2

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

GnomAD2 exomes

AF:

0.000213

AC:

AN:

155136

AF XY:

0.000248

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 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

African (AFR)

AF:

0.000280

AC:

AN:

32184

American (AMR)

AF:

0.000136

AC:

AN:

36842

Ashkenazi Jewish (ASJ)

AF:

0.000596

AC:

AN:

25162

East Asian (EAS)

AF:

0.00

AC:

AN:

36646

South Asian (SAS)

AF:

0.0000621

AC:

AN:

80536

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43254

Middle Eastern (MID)

AF:

0.00610

AC:

AN:

5408

European-Non Finnish (NFE)

AF:

0.000126

AC:

137

AN:

1085554

Other (OTH)

AF:

0.000274

AC:

AN:

58356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000151

AC:

AN:

151922

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41498

American (AMR)

AF:

0.000393

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.000578

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5128

South Asian (SAS)

AF:

0.000208

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10520

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

67896

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000406

Hom.:

Bravo

AF:

0.000291

ExAC

AF:

0.000148

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.35

DEOGEN2

Benign

0.19

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.25

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.65

M_CAP

Benign

0.0066

MetaRNN

Benign

0.032

MetaSVM

Benign

-0.98

PhyloP100

2.4

PrimateAI

Uncertain

0.57

PROVEAN

Benign

0.52

REVEL

Benign

0.064

Sift

Benign

0.96

Sift4G

Benign

0.56

Polyphen

0.0

Vest4

0.23

MVP

0.24

MPC

0.47

ClinPred

0.030

GERP RS

4.5

PromoterAI

-0.021

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.19

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over