22-38294408-C-T

Variant names:

• chr22-38294408-C-T
• NM_152221.3:c.1012G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152221.3(CSNK1E):​c.1012G>A​(p.Ala338Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000712 in 1,405,274 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: CSNK1E NM_152221.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.14
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14889309).

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.1012G>A	p.Ala338Thr	missense	Exon 8 of 11	NP_689407.1	P49674
	TPTEP2-CSNK1E	NM_001289912.2		c.1012G>A	p.Ala338Thr	missense	Exon 12 of 15	NP_001276841.1
	CSNK1E	NM_001894.5		c.1012G>A	p.Ala338Thr	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.1012G>A	p.Ala338Thr	missense	Exon 8 of 11	ENSP00000380044.1	P49674
	CSNK1E	ENST00000359867.7	TSL:1	c.1012G>A	p.Ala338Thr	missense	Exon 8 of 11	ENSP00000352929.3	P49674
	TPTEP2-CSNK1E	ENST00000400206.7	TSL:2	c.1012G>A	p.Ala338Thr	missense	Exon 12 of 15	ENSP00000383067.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.12e-7 AC: 1 AN: 1405274 Hom.: 0 Cov.: 35 AF XY: 0.00000144 AC XY: 1 AN XY: 694666

African (AFR) AF: 0.00 AC: 0 AN: 32102

American (AMR) AF: 0.00 AC: 0 AN: 37048

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25172

East Asian (EAS) AF: 0.00 AC: 0 AN: 36506

South Asian (SAS) AF: 0.00 AC: 0 AN: 80600

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44318

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5422

European-Non Finnish (NFE) AF: 9.21e-7 AC: 1 AN: 1085750

Other (OTH) AF: 0.00 AC: 0 AN: 58356

GnomAD4 genome Cov.: 32

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	0.067
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.035
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
PhyloP100		2.1
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.036
Sift	Benign	0.33	T
Sift4G	Benign	0.44	T
Polyphen		0.0010	B
Vest4		0.26
MutPred		0.21		Gain of phosphorylation at A338 (P = 0.0262)
MVP		0.32
MPC		0.50
ClinPred		0.72	D
GERP RS		3.3
PromoterAI		-0.0056	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.034
gMVP		0.44
Mutation Taster		=87/13	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

hg19: chr22-38690414;