22-38294393-T-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM1 BP4_Strong BS2

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. 13/20 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.38

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:):

ACMG classification

Verdict is Likely_benign. Variant got -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 GnomAd at 23 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSNK1E	NM_152221.3	c.1027A>G	p.Ser343Gly	missense_variant	8/11	ENST00000396832.6
TPTEP2-CSNK1E	NM_001289912.2	c.1027A>G	p.Ser343Gly	missense_variant	12/15
CSNK1E	NM_001894.5	c.1027A>G	p.Ser343Gly	missense_variant	8/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSNK1E	ENST00000396832.6	c.1027A>G	p.Ser343Gly	missense_variant	8/11	1	NM_152221.3	P1

Frequencies

GnomAD3 genomes AF: 0.000152 AC: 23 AN: 151796 Hom.: 0 Cov.: 32

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

GnomAD3 exomes AF: 0.000213 AC: 33 AN: 155136 Hom.: 1 AF XY: 0.000248 AC XY: 21 AN XY: 84804

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 SAS exome AF: 0.000126

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.: 2 Cov.: 35 AF XY: 0.000163 AC XY: 113 AN XY: 693818

Gnomad4 AFR exome AF: 0.000280

Gnomad4 AMR exome AF: 0.000136

Gnomad4 ASJ exome AF: 0.000596

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000621

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000126

Gnomad4 OTH exome AF: 0.000274

GnomAD4 genome AF: 0.000151 AC: 23 AN: 151922 Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8 AN XY: 74294

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000393

Gnomad4 ASJ AF: 0.000578

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.000406 Hom.: 1

Bravo AF: 0.000291

ExAC AF: 0.000148 AC: 17

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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

Aug 14, 2023

The c.1027A>G (p.S343G) alteration is located in exon 8 (coding exon 7) of the CSNK1E gene. This alteration results from a A to G substitution at nucleotide position 1027, causing the serine (S) at amino acid position 343 to be replaced by a glycine (G). 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	0.055
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.59
Cadd	Benign	17
Dann	Benign	0.35
DEOGEN2	Benign	0.19	T;T;T;.
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.25
FATHMM_MKL	Uncertain	0.88	D
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.032	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	0.90	N;N;N;N;N
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	0.52	N;N;N;N
REVEL	Benign	0.064
Sift	Benign	0.96	T;T;T;T
Sift4G	Benign	0.56	T;T;T;T
Polyphen		0.0	B;B;B;.
Vest4		0.23
MVP		0.24
MPC		0.47
ClinPred		0.030	T
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.19

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: rs369141815; hg19: chr22-38690399;