5-149495744-TAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAAAAA

Variant names:

• chr5-149495744-T-TAAAAAAAAAA
• rs149346325
• NM_001892.6:c.*1099_*1108dupTTTTTTTTTT

Variant summary

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

The NM_001892.6(CSNK1A1):​c.*1099_*1108dupTTTTTTTTTT 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 0.0059 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0 (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.*1099_*1108dupTTTTTTTTTT		3_prime_UTR	Exon 10 of 10	NP_001883.4
	CSNK1A1	NM_001025105.3		c.*1099_*1108dupTTTTTTTTTT		3_prime_UTR	Exon 11 of 11	NP_001020276.1	P48729-2
	CSNK1A1	NM_001271741.2		c.*1099_*1108dupTTTTTTTTTT		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.*1099_*1108dupTTTTTTTTTT		3_prime_UTR	Exon 10 of 10	ENSP00000367074.2	P48729-1
	CSNK1A1	ENST00000261798.10	TSL:1	c.*1099_*1108dupTTTTTTTTTT		3_prime_UTR	Exon 11 of 11	ENSP00000261798.6	P48729-2
	ENSG00000230551	ENST00000499521.2	TSL:1	n.7196_7205dupTTTTTTTTTT		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.00587 AC: 536 AN: 91274 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00702

Gnomad AMI AF: 0.00503

Gnomad AMR AF: 0.00335

Gnomad ASJ AF: 0.00875

Gnomad EAS AF: 0.00685

Gnomad SAS AF: 0.00152

Gnomad FIN AF: 0.000900

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00616

Gnomad OTH AF: 0.00334

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 194 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 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: 0.00 AC: 0 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: 0.00587 AC: 536 AN: 91254 Hom.: 0 Cov.: 0 AF XY: 0.00572 AC XY: 243 AN XY: 42516

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

African (AFR) AF: 0.00701 AC: 179 AN: 25536

American (AMR) AF: 0.00335 AC: 26 AN: 7756

Ashkenazi Jewish (ASJ) AF: 0.00875 AC: 22 AN: 2514

East Asian (EAS) AF: 0.00687 AC: 22 AN: 3202

South Asian (SAS) AF: 0.00153 AC: 4 AN: 2610

European-Finnish (FIN) AF: 0.000900 AC: 3 AN: 3334

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 174

European-Non Finnish (NFE) AF: 0.00616 AC: 273 AN: 44332

Other (OTH) AF: 0.00333 AC: 4 AN: 1200

⚠️ 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;