5-149505465-T-A

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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. 15/21 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

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

Verdict is Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSNK1A1	NM_001892.6	c.988A>T	p.Thr330Ser	missense_variant	Exon 9 of 10	ENST00000377843.8	NP_001883.4
CSNK1A1	NM_001025105.3	c.1072A>T	p.Thr358Ser	missense_variant	Exon 10 of 11		NP_001020276.1
CSNK1A1	NM_001271742.2	c.805A>T	p.Thr269Ser	missense_variant	Exon 9 of 10		NP_001258671.1
CSNK1A1	NM_001271741.2	c.970+18A>T		intron_variant	Intron 9 of 9		NP_001258670.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSNK1A1	ENST00000377843.8	c.988A>T	p.Thr330Ser	missense_variant	Exon 9 of 10	1	NM_001892.6	ENSP00000367074.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1072A>T (p.T358S) alteration is located in exon 10 (coding exon 10) of the CSNK1A1 gene. This alteration results from a A to T substitution at nucleotide position 1072, causing the threonine (T) at amino acid position 358 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T;.;T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.48	T;.;T;.
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.055	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.49	N;.;.;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.17	N;.;N;.
REVEL	Benign	0.092
Sift	Benign	0.52	T;.;T;.
Sift4G	Benign	0.77	T;T;T;T
Polyphen		0.0	B;.;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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-148885028;