5-149495744-TAAAAAAAAAAA-TAAAAAAAAAAAAAA

Variant names:

• chr5-149495744-T-TAAA
• rs149346325
• NM_001892.6:c.*1106_*1108dupTTT

Variant summary

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

The NM_001892.6(CSNK1A1):​c.*1106_*1108dupTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.000086 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0052 (0 hom.)
  • Failed GnomAD Quality Control
• 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.*1106_*1108dupTTT		3_prime_UTR	Exon 10 of 10	NP_001883.4
	CSNK1A1	NM_001025105.3		c.*1106_*1108dupTTT		3_prime_UTR	Exon 11 of 11	NP_001020276.1	P48729-2
	CSNK1A1	NM_001271741.2		c.*1106_*1108dupTTT		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.*1106_*1108dupTTT		3_prime_UTR	Exon 10 of 10	ENSP00000367074.2	P48729-1
	CSNK1A1	ENST00000261798.10	TSL:1	c.*1106_*1108dupTTT		3_prime_UTR	Exon 11 of 11	ENSP00000261798.6	P48729-2
	ENSG00000230551	ENST00000499521.2	TSL:1	n.7203_7205dupTTT		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0000864 AC: 8 AN: 92556 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000128

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000310

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000133

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00515 AC: 1 AN: 194 Hom.: 0 Cov.: 0 AF XY: 0.00862 AC XY: 1 AN XY: 116

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00521 AC: 1 AN: 192

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.0000865 AC: 8 AN: 92536 Hom.: 0 Cov.: 0 AF XY: 0.0000465 AC XY: 2 AN XY: 43018

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

African (AFR) AF: 0.00 AC: 0 AN: 25898

American (AMR) AF: 0.000128 AC: 1 AN: 7816

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2586

East Asian (EAS) AF: 0.000311 AC: 1 AN: 3214

South Asian (SAS) AF: 0.00 AC: 0 AN: 2622

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3340

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 176

European-Non Finnish (NFE) AF: 0.000133 AC: 6 AN: 45052

Other (OTH) AF: 0.00 AC: 0 AN: 1218

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000259213), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

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;