22-38302851-G-C

Variant names:

• chr22-38302851-G-C
• rs186918102
• NM_152221.3:c.336+10C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152221.3(CSNK1E):​c.336+10C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,474 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CSNK1E NM_152221.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.438

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSNK1E	NM_152221.3	c.336+10C>G		intron_variant	Intron 4 of 10	ENST00000396832.6	NP_689407.1
TPTEP2-CSNK1E	NM_001289912.2	c.336+10C>G		intron_variant	Intron 8 of 14		NP_001276841.1
CSNK1E	NM_001894.5	c.336+10C>G		intron_variant	Intron 4 of 10		NP_001885.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSNK1E	ENST00000396832.6	c.336+10C>G		intron_variant	Intron 4 of 10	1	NM_152221.3	ENSP00000380044.1
TPTEP2-CSNK1E	ENST00000400206.7	c.336+10C>G		intron_variant	Intron 8 of 14	2		ENSP00000383067.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000120 AC: 3 AN: 250570 Hom.: 0 AF XY: 0.0000221 AC XY: 3 AN XY: 135552

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000265

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461474 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 727006

Gnomad4 AFR exome AF: 0.00

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000252 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.5
DANN	Benign	0.66

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: rs186918102; hg19: chr22-38698856;