5-149495744-TAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAAAAAAAA

Variant names:

• chr5-149495744-T-TAAAAAAAAAAAAA
• rs149346325
• NM_001892.6:c.*1096_*1108dupTTTTTTTTTTTTT

Variant summary

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

The NM_001892.6(CSNK1A1):​c.*1096_*1108dupTTTTTTTTTTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.00084 (0 hom., cov: 0)
• Consequence: CSNK1A1 NM_001892.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.157
• Publications: 0 publications found

Genes affected

CSNK1A1 (HGNC:2451): (casein kinase 1 alpha 1) Enables protein serine/threonine kinase activity. Involved in several processes, including negative regulation of canonical Wnt signaling pathway; peptidyl-serine phosphorylation; and positive regulation of proteasomal ubiquitin-dependent protein catabolic process. Located in centrosome; cytosol; and nuclear speck. Part of beta-catenin destruction complex. Colocalizes with keratin filament and mRNA cleavage and polyadenylation specificity factor complex. Biomarker of Alzheimer's disease and inclusion body myositis. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000230551 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001892.6. 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
	CSNK1A1	NM_001892.6	MANE Select	c.*1096_*1108dupTTTTTTTTTTTTT		3_prime_UTR	Exon 10 of 10	NP_001883.4
	CSNK1A1	NM_001025105.3		c.*1096_*1108dupTTTTTTTTTTTTT		3_prime_UTR	Exon 11 of 11	NP_001020276.1	P48729-2
	CSNK1A1	NM_001271741.2		c.*1096_*1108dupTTTTTTTTTTTTT		3_prime_UTR	Exon 10 of 10	NP_001258670.1	P48729-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSNK1A1	ENST00000377843.8	TSL:1 MANE Select	c.*1096_*1108dupTTTTTTTTTTTTT		3_prime_UTR	Exon 10 of 10	ENSP00000367074.2	P48729-1
	CSNK1A1	ENST00000261798.10	TSL:1	c.*1096_*1108dupTTTTTTTTTTTTT		3_prime_UTR	Exon 11 of 11	ENSP00000261798.6	P48729-2
	ENSG00000230551	ENST00000499521.2	TSL:1	n.7193_7205dupTTTTTTTTTTTTT		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.000845 AC: 78 AN: 92338 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000814

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000642

Gnomad ASJ AF: 0.000387

Gnomad EAS AF: 0.00124

Gnomad SAS AF: 0.000379

Gnomad FIN AF: 0.000300

Gnomad MID AF: 0.00505

Gnomad NFE AF: 0.000957

Gnomad OTH AF: 0.000826

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.000845 AC: 78 AN: 92318 Hom.: 0 Cov.: 0 AF XY: 0.000909 AC XY: 39 AN XY: 42908

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000812 AC: 21 AN: 25848

American (AMR) AF: 0.000641 AC: 5 AN: 7796

Ashkenazi Jewish (ASJ) AF: 0.000387 AC: 1 AN: 2582

East Asian (EAS) AF: 0.00124 AC: 4 AN: 3218

South Asian (SAS) AF: 0.000382 AC: 1 AN: 2618

European-Finnish (FIN) AF: 0.000300 AC: 1 AN: 3334

Middle Eastern (MID) AF: 0.00568 AC: 1 AN: 176

European-Non Finnish (NFE) AF: 0.000957 AC: 43 AN: 44922

Other (OTH) AF: 0.000825 AC: 1 AN: 1212

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.16

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs149346325; hg19: chr5-148875307;