chr22-38300904-C-T

Position:

• chr22-38300904-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_152221.3(CSNK1E):​c.385G>A​(p.Val129Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000821 in 1,461,882 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: 33)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: CSNK1E NM_152221.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.72

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1740557).
• BS2: High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSNK1E	NM_152221.3	c.385G>A	p.Val129Ile	missense_variant	5/11	ENST00000396832.6	NP_689407.1
TPTEP2-CSNK1E	NM_001289912.2	c.385G>A	p.Val129Ile	missense_variant	9/15		NP_001276841.1
CSNK1E	NM_001894.5	c.385G>A	p.Val129Ile	missense_variant	5/11		NP_001885.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSNK1E	ENST00000396832.6	c.385G>A	p.Val129Ile	missense_variant	5/11	1	NM_152221.3	ENSP00000380044.1
TPTEP2-CSNK1E	ENST00000400206.7	c.385G>A	p.Val129Ile	missense_variant	9/15	2		ENSP00000383067.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461882 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8 AN XY: 727240

Gnomad4 AFR exome AF: 0.000149

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000629

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 28, 2024

The c.385G>A (p.V129I) alteration is located in exon 5 (coding exon 4) of the CSNK1E gene. This alteration results from a G to A substitution at nucleotide position 385, causing the valine (V) at amino acid position 129 to be replaced by an isoleucine (I). 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	0.092
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	22
DANN	Benign	0.58
DEOGEN2	Benign	0.12	T;T;T;T;T;.;.
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.89	.;D;.;D;D;D;.
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.17	T;T;T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-1.5	N;N;N;.;.;.;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	0.40	N;N;N;N;N;N;N
REVEL	Benign	0.15
Sift	Benign	1.0	T;T;T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T;T;T
Polyphen		0.0010	B;B;B;B;B;.;.
Vest4		0.28
MutPred		0.50		Gain of catalytic residue at P131 (P = 0.03);Gain of catalytic residue at P131 (P = 0.03);Gain of catalytic residue at P131 (P = 0.03);Gain of catalytic residue at P131 (P = 0.03);Gain of catalytic residue at P131 (P = 0.03);Gain of catalytic residue at P131 (P = 0.03);Gain of catalytic residue at P131 (P = 0.03);
MVP		0.18
MPC		1.2
ClinPred		0.72	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.073
gMVP		0.74

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

Other links and lift over

dbSNP: rs1644459774; hg19: chr22-38696909; COSMIC: COSV100725012; COSMIC: COSV100725012;