22-38300173-G-C

Variant names:

• chr22-38300173-G-C
• rs6001090
• NM_152221.3:c.566-108C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152221.3(CSNK1E):​c.566-108C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000114 in 877,366 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: 0.0000011 (0 hom.)
• Consequence: CSNK1E NM_152221.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.658
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

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.566-108C>G		intron	N/A	NP_689407.1	P49674
	TPTEP2-CSNK1E	NM_001289912.2		c.566-108C>G		intron	N/A	NP_001276841.1
	CSNK1E	NM_001894.5		c.566-108C>G		intron	N/A	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.566-108C>G		intron	N/A	ENSP00000380044.1	P49674
	CSNK1E	ENST00000359867.7	TSL:1	c.566-108C>G		intron	N/A	ENSP00000352929.3	P49674
	TPTEP2-CSNK1E	ENST00000400206.7	TSL:2	c.566-108C>G		intron	N/A	ENSP00000383067.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000114 AC: 1 AN: 877366 Hom.: 0 AF XY: 0.00000226 AC XY: 1 AN XY: 442106

African (AFR) AF: 0.00 AC: 0 AN: 20366

American (AMR) AF: 0.00 AC: 0 AN: 23476

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17394

East Asian (EAS) AF: 0.00 AC: 0 AN: 33520

South Asian (SAS) AF: 0.00 AC: 0 AN: 58022

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34824

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3988

European-Non Finnish (NFE) AF: 0.00000155 AC: 1 AN: 645618

Other (OTH) AF: 0.00 AC: 0 AN: 40158

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 933

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.15
DANN	Benign	0.30
PhyloP100		-0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

dbSNP: rs6001090; hg19: chr22-38696178;