13-37104913-A-T

Variant names:

• chr13-37104913-A-T
• rs183000285
• NM_145203.6:c.344T>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_145203.6(CSNK1A1L):​c.344T>A​(p.Met115Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M115R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CSNK1A1L NM_145203.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.60
• Publications: 2 publications found

Genes affected

CSNK1A1L (HGNC:20289): (casein kinase 1 alpha 1 like) Predicted to enable protein serine/threonine kinase activity. Predicted to be involved in negative regulation of canonical Wnt signaling pathway and peptidyl-serine phosphorylation. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000307674 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.783

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145203.6. 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
	CSNK1A1L	NM_145203.6	MANE Select	c.344T>A	p.Met115Lys	missense	Exon 1 of 1	NP_660204.2	Q8N752

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSNK1A1L	ENST00000379800.4	TSL:6 MANE Select	c.344T>A	p.Met115Lys	missense	Exon 1 of 1	ENSP00000369126.3	Q8N752
	ENSG00000307674	ENST00000827791.1		n.693A>T		non_coding_transcript_exon	Exon 2 of 2
	ENSG00000307674	ENST00000827800.1		n.683A>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461894 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Uncertain	0.075	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.40
Eigen_PC	Benign	0.17
FATHMM_MKL	Benign	0.70	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0022	T
MetaRNN	Pathogenic	0.78	D
MetaSVM	Benign	-0.41	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		6.6
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Uncertain	0.38
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.64
MutPred		0.57		Gain of catalytic residue at M115 (P = 0.0101)
MVP		0.97
MPC		0.86
ClinPred		1.0	D
GERP RS		-0.23
Varity_R		0.97
gMVP		0.34
Mutation Taster		=89/11	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

dbSNP: rs183000285; hg19: chr13-37679050;