chr22-38294347-G-A

Variant names:

• chr22-38294347-G-A
• rs200714722
• NM_152221.3:c.1073C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

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. 15/21 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.21
• Publications: 1 publications found

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]

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]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07541984).
• BS2: High AC in GnomAd4 at 15 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSNK1E	NM_152221.3	MANE Select	c.1073C>T	p.Pro358Leu	missense	Exon 8 of 11	NP_689407.1	P49674
	TPTEP2-CSNK1E	NM_001289912.2		c.1073C>T	p.Pro358Leu	missense	Exon 12 of 15	NP_001276841.1
	CSNK1E	NM_001894.5		c.1073C>T	p.Pro358Leu	missense	Exon 8 of 11	NP_001885.1	P49674

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSNK1E	ENST00000396832.6	TSL:1 MANE Select	c.1073C>T	p.Pro358Leu	missense	Exon 8 of 11	ENSP00000380044.1	P49674
	CSNK1E	ENST00000359867.7	TSL:1	c.1073C>T	p.Pro358Leu	missense	Exon 8 of 11	ENSP00000352929.3	P49674
	TPTEP2-CSNK1E	ENST00000400206.7	TSL:2	c.1073C>T	p.Pro358Leu	missense	Exon 12 of 15	ENSP00000383067.2

Frequencies

GnomAD3 genomes AF: 0.0000996 AC: 15 AN: 150672 Hom.: 0 Cov.: 32

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

GnomAD2 exomes AF: 0.000131 AC: 24 AN: 183002 AF XY: 0.000139

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 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.: 0 Cov.: 35 AF XY: 0.000136 AC XY: 95 AN XY: 697830

African (AFR) AF: 0.0000612 AC: 2 AN: 32678

American (AMR) AF: 0.0000772 AC: 3 AN: 38880

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24848

East Asian (EAS) AF: 0.00 AC: 0 AN: 37752

South Asian (SAS) AF: 0.0000365 AC: 3 AN: 82184

European-Finnish (FIN) AF: 0.0000244 AC: 1 AN: 40994

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5536

European-Non Finnish (NFE) AF: 0.000165 AC: 180 AN: 1088458

Other (OTH) AF: 0.000120 AC: 7 AN: 58176

GnomAD4 genome AF: 0.0000995 AC: 15 AN: 150800 Hom.: 0 Cov.: 32 AF XY: 0.000122 AC XY: 9 AN XY: 73674

African (AFR) AF: 0.0000242 AC: 1 AN: 41316

American (AMR) AF: 0.00 AC: 0 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5006

South Asian (SAS) AF: 0.00 AC: 0 AN: 4672

European-Finnish (FIN) AF: 0.0000982 AC: 1 AN: 10186

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000192 AC: 13 AN: 67666

Other (OTH) AF: 0.00 AC: 0 AN: 2102

Alfa AF: 0.000583 Hom.: 0

Bravo AF: 0.000121

ExAC AF: 0.0000924 AC: 11

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	19
DANN	Benign	0.69
DEOGEN2	Benign	0.40	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.086
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-1.0	T
PhyloP100		2.2
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.059
Sift	Benign	0.36	T
Sift4G	Benign	0.16	T
Polyphen		0.044	B
Vest4		0.18
MVP		0.44
MPC		0.53
ClinPred		0.076	T
GERP RS		4.5
PromoterAI		0.023	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.062
gMVP		0.11
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs200714722; hg19: chr22-38690353;