5-149505494-T-A

Variant names:

• chr5-149505494-T-A
• NM_001892.6:c.959A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001892.6(CSNK1A1):​c.959A>T​(p.Gln320Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 7.67

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23237333).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSNK1A1	NM_001892.6	c.959A>T	p.Gln320Leu	missense_variant	Exon 9 of 10	ENST00000377843.8	NP_001883.4
CSNK1A1	NM_001025105.3	c.1043A>T	p.Gln348Leu	missense_variant	Exon 10 of 11		NP_001020276.1
CSNK1A1	NM_001271741.2	c.959A>T	p.Gln320Leu	missense_variant	Exon 9 of 10		NP_001258670.1
CSNK1A1	NM_001271742.2	c.776A>T	p.Gln259Leu	missense_variant	Exon 9 of 10		NP_001258671.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSNK1A1	ENST00000377843.8	c.959A>T	p.Gln320Leu	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

Dec 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1043A>T (p.Q348L) 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 1043, causing the glutamine (Q) at amino acid position 348 to be replaced by a leucine (L). 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	0.085
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.063	.;T;T;T;T;.;T
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D;D;D;D;.;D;.
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.23	T;T;T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.1	M;M;.;.;.;.;.
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-1.4	N;N;N;N;.;N;.
REVEL	Benign	0.17
Sift	Benign	0.15	T;T;T;T;.;T;.
Sift4G	Benign	0.32	T;T;T;T;T;T;T
Polyphen		0.0010, 0.0, 0.72, 0.79	.;B;B;P;.;P;.
Vest4		0.55
MutPred		0.23		Loss of solvent accessibility (P = 0.0468);Loss of solvent accessibility (P = 0.0468);.;.;.;.;.;
MVP		0.40
MPC		3.0
ClinPred		0.86	D
GERP RS		5.4
Varity_R		0.19
gMVP		0.71

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: chr5-148885057;