5-149495744-TAAAAAAAAAAA-TAAAAAAAAAAAAA

Variant names:

• chr5-149495744-T-TAA
• rs149346325
• NM_001892.6:c.*1107_*1108dupTT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001892.6(CSNK1A1):​c.*1107_*1108dupTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0053 (10 hom., cov: 0)
  • Exomes 𝑓: 0.010 (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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 491 AD gene.

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.*1107_*1108dupTT		3_prime_UTR	Exon 10 of 10	NP_001883.4
	CSNK1A1	NM_001025105.3		c.*1107_*1108dupTT		3_prime_UTR	Exon 11 of 11	NP_001020276.1	P48729-2
	CSNK1A1	NM_001271741.2		c.*1107_*1108dupTT		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.*1107_*1108dupTT		3_prime_UTR	Exon 10 of 10	ENSP00000367074.2	P48729-1
	CSNK1A1	ENST00000261798.10	TSL:1	c.*1107_*1108dupTT		3_prime_UTR	Exon 11 of 11	ENSP00000261798.6	P48729-2
	ENSG00000230551	ENST00000499521.2	TSL:1	n.7204_7205dupTT		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.00531 AC: 491 AN: 92528 Hom.: 10 Cov.: 0

Gnomad AFR AF: 0.00878

Gnomad AMI AF: 0.00163

Gnomad AMR AF: 0.00333

Gnomad ASJ AF: 0.000387

Gnomad EAS AF: 0.00279

Gnomad SAS AF: 0.00114

Gnomad FIN AF: 0.0204

Gnomad MID AF: 0.00505

Gnomad NFE AF: 0.00331

Gnomad OTH AF: 0.00493

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0103 AC: 2 AN: 194 Hom.: 0 Cov.: 0 AF XY: 0.00862 AC XY: 1 AN XY: 116

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

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: 0.0104 AC: 2 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

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0296732), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00531 AC: 491 AN: 92508 Hom.: 10 Cov.: 0 AF XY: 0.00602 AC XY: 259 AN XY: 43022

African (AFR) AF: 0.00877 AC: 227 AN: 25894

American (AMR) AF: 0.00333 AC: 26 AN: 7814

Ashkenazi Jewish (ASJ) AF: 0.000387 AC: 1 AN: 2584

East Asian (EAS) AF: 0.00280 AC: 9 AN: 3214

South Asian (SAS) AF: 0.00115 AC: 3 AN: 2620

European-Finnish (FIN) AF: 0.0204 AC: 68 AN: 3340

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

European-Non Finnish (NFE) AF: 0.00331 AC: 149 AN: 45034

Other (OTH) AF: 0.00493 AC: 6 AN: 1218

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
Mutation Taster		=100/0	polymorphism

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;