5-149495744-TAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAAAA

Variant names:

• chr5-149495744-T-TAAAAAAAAA
• rs149346325
• NM_001892.6:c.*1100_*1108dupTTTTTTTTT

Variant summary

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

The NM_001892.6(CSNK1A1):​c.*1100_*1108dupTTTTTTTTT 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 0.0079 (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.*1100_*1108dupTTTTTTTTT		3_prime_UTR	Exon 10 of 10	NP_001883.4
	CSNK1A1	NM_001025105.3		c.*1100_*1108dupTTTTTTTTT		3_prime_UTR	Exon 11 of 11	NP_001020276.1	P48729-2
	CSNK1A1	NM_001271741.2		c.*1100_*1108dupTTTTTTTTT		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.*1100_*1108dupTTTTTTTTT		3_prime_UTR	Exon 10 of 10	ENSP00000367074.2	P48729-1
	CSNK1A1	ENST00000261798.10	TSL:1	c.*1100_*1108dupTTTTTTTTT		3_prime_UTR	Exon 11 of 11	ENSP00000261798.6	P48729-2
	ENSG00000230551	ENST00000499521.2	TSL:1	n.7197_7205dupTTTTTTTTT		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.00787 AC: 714 AN: 90680 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00703

Gnomad AMI AF: 0.00503

Gnomad AMR AF: 0.00674

Gnomad ASJ AF: 0.00750

Gnomad EAS AF: 0.00889

Gnomad SAS AF: 0.00807

Gnomad FIN AF: 0.00362

Gnomad MID AF: 0.0104

Gnomad NFE AF: 0.00886

Gnomad OTH AF: 0.00753

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR 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: 0.00788 AC: 714 AN: 90660 Hom.: 0 Cov.: 0 AF XY: 0.00802 AC XY: 339 AN XY: 42244

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

African (AFR) AF: 0.00702 AC: 179 AN: 25512

American (AMR) AF: 0.00674 AC: 52 AN: 7714

Ashkenazi Jewish (ASJ) AF: 0.00750 AC: 19 AN: 2532

East Asian (EAS) AF: 0.00893 AC: 28 AN: 3136

South Asian (SAS) AF: 0.00813 AC: 21 AN: 2584

European-Finnish (FIN) AF: 0.00362 AC: 12 AN: 3316

Middle Eastern (MID) AF: 0.0116 AC: 2 AN: 172

European-Non Finnish (NFE) AF: 0.00886 AC: 389 AN: 43900

Other (OTH) AF: 0.00751 AC: 9 AN: 1198

⚠️ 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;