13-37104853-C-G

Variant names:

• chr13-37104853-C-G
• rs775483694
• NM_145203.6:c.404G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_145203.6(CSNK1A1L):​c.404G>C​(p.Arg135Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,878 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. R135Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: CSNK1A1L NM_145203.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.66
• Publications: 0 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.923

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.404G>C	p.Arg135Pro	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.404G>C	p.Arg135Pro	missense	Exon 1 of 1	ENSP00000369126.3	Q8N752
	ENSG00000307674	ENST00000827791.1		n.633C>G		non_coding_transcript_exon	Exon 2 of 2
	ENSG00000307674	ENST00000827800.1		n.623C>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461878 Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6 AN XY: 727242

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: 53410

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

European-Non Finnish (NFE) AF: 0.00000809 AC: 9 AN: 1112006

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	1.0
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.24
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	T
Eigen	Uncertain	0.56
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.0033	T
MetaRNN	Pathogenic	0.92	D
MetaSVM	Uncertain	0.13	D
MutationAssessor	Pathogenic	6.4	H
PhyloP100		5.7
PrimateAI	Benign	0.37	T
PROVEAN	Pathogenic	-6.9	D
REVEL	Uncertain	0.55
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.79
MutPred		0.77		Gain of catalytic residue at F132 (P = 0.001)
MVP		0.90
MPC		0.87
ClinPred		1.0	D
GERP RS		0.091
Varity_R		0.97
gMVP		0.79
Mutation Taster		=81/19	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: rs775483694; hg19: chr13-37678990;