13-37104604-C-G

Variant names:

• chr13-37104604-C-G
• rs111625960
• NM_145203.6:c.653G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145203.6(CSNK1A1L):​c.653G>C​(p.Ser218Thr) 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. 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. S218N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CSNK1A1L NM_145203.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.392
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.108245194).

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.653G>C	p.Ser218Thr	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.653G>C	p.Ser218Thr	missense	Exon 1 of 1	ENSP00000369126.3	Q8N752
	ENSG00000307674	ENST00000827784.1		n.80C>G		non_coding_transcript_exon	Exon 2 of 5
	ENSG00000307674	ENST00000827785.1		n.63C>G		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.9
DANN	Benign	0.68
DEOGEN2	Benign	0.030	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.39
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.12
Sift	Benign	0.11	T
Sift4G	Benign	0.11	T
Polyphen		0.0050	B
Vest4		0.17
MutPred		0.54		Gain of catalytic residue at L219 (P = 0)
MVP		0.19
MPC		0.16
ClinPred		0.20	T
GERP RS		-2.1
Varity_R		0.18
gMVP		0.12
Mutation Taster		=95/5	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: rs111625960; hg19: chr13-37678741;