22-38293315-C-T

Variant names:

• chr22-38293315-C-T
• rs77945315
• NM_152221.3:c.1223G>A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM1 BP4_Strong BS1 BS2

The NM_152221.3(CSNK1E):​c.1223G>A​(p.Ser408Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00112 in 1,606,320 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00051 (5 hom., cov: 31)
  • Exomes 𝑓: 0.0012 (62 hom.)
• Consequence: CSNK1E NM_152221.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.71

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

Verdict is Benign. Variant got -10 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity KC1E_HUMAN
• BP4: Computational evidence support a benign effect (MetaRNN=0.008904189).
• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00118 (1723/1454306) while in subpopulation EAS AF= 0.0432 (1710/39584). AF 95% confidence interval is 0.0415. There are 62 homozygotes in gnomad4_exome. There are 840 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 77 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSNK1E	NM_152221.3	c.1223G>A	p.Ser408Asn	missense_variant	Exon 10 of 11	ENST00000396832.6	NP_689407.1
TPTEP2-CSNK1E	NM_001289912.2	c.1223G>A	p.Ser408Asn	missense_variant	Exon 14 of 15		NP_001276841.1
CSNK1E	NM_001894.5	c.1223G>A	p.Ser408Asn	missense_variant	Exon 10 of 11		NP_001885.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSNK1E	ENST00000396832.6	c.1223G>A	p.Ser408Asn	missense_variant	Exon 10 of 11	1	NM_152221.3	ENSP00000380044.1
TPTEP2-CSNK1E	ENST00000400206.7	c.1223G>A	p.Ser408Asn	missense_variant	Exon 14 of 15	2		ENSP00000383067.2

Frequencies

GnomAD3 genomes AF: 0.000507 AC: 77 AN: 151896 Hom.: 5 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0147

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000481

GnomAD3 exomes AF: 0.000191 AC: 47 AN: 246716 Hom.: 0 AF XY: 0.000187 AC XY: 25 AN XY: 133478

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00241

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000499

GnomAD4 exome AF: 0.00118 AC: 1723 AN: 1454306 Hom.: 62 Cov.: 30 AF XY: 0.00116 AC XY: 840 AN XY: 723596

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0432

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.000200

GnomAD4 genome AF: 0.000507 AC: 77 AN: 152014 Hom.: 5 Cov.: 31 AF XY: 0.000552 AC XY: 41 AN XY: 74284

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0148

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000476

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.000121

ExAC AF: 0.000321 AC: 39

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T;T;T;.
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.86	.;D;.;.
MetaRNN	Benign	0.0089	T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-0.57	N;N;N;N
REVEL	Benign	0.062
Sift	Uncertain	0.0030	D;D;D;D
Sift4G	Benign	0.12	T;T;T;T
Polyphen		0.36	B;B;B;.
Vest4		0.76
MVP		0.60
MPC		1.0
ClinPred		0.15	T
GERP RS		5.8
Varity_R		0.19
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs77945315; hg19: chr22-38689321;