chr5-149505465-T-A

Variant names:

• chr5-149505465-T-A
• NM_001892.6:c.988A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001892.6(CSNK1A1):​c.988A>T​(p.Thr330Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CSNK1A1 NM_001892.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.22
• 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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054618746).

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.988A>T	p.Thr330Ser	missense	Exon 9 of 10	NP_001883.4
	CSNK1A1	NM_001025105.3		c.1072A>T	p.Thr358Ser	missense	Exon 10 of 11	NP_001020276.1	P48729-2
	CSNK1A1	NM_001271742.2		c.805A>T	p.Thr269Ser	missense	Exon 9 of 10	NP_001258671.1	B4DER9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSNK1A1	ENST00000377843.8	TSL:1 MANE Select	c.988A>T	p.Thr330Ser	missense	Exon 9 of 10	ENSP00000367074.2	P48729-1
	CSNK1A1	ENST00000261798.10	TSL:1	c.1072A>T	p.Thr358Ser	missense	Exon 10 of 11	ENSP00000261798.6	P48729-2
	CSNK1A1	ENST00000606719.6	TSL:2	c.1081A>T	p.Thr361Ser	missense	Exon 10 of 11	ENSP00000475319.2	U3KPX3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	22
DANN	Benign	0.87
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.49	N
PhyloP100		3.2
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.092
Sift	Benign	0.52	T
Sift4G	Benign	0.77	T
Polyphen		0.0	B
Vest4		0.15
MutPred		0.15		Loss of methylation at K331 (P = 0.1254)
MVP		0.56
MPC		1.5
ClinPred		0.29	T
GERP RS		4.2
Varity_R		0.032
gMVP		0.28
Mutation Taster		=74/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

hg19: chr5-148885028;