rs56224973

Variant names:

• chr13-37105244-T-A
• rs56224973
• NM_145203.6:c.13A>T

Your query was ambiguous. Multiple possible variants found:

• chr13-37105244-T-A
• chr13-37105244-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_145203.6(CSNK1A1L):​c.13A>T​(p.Ser5Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00029 in 1,608,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00030 (0 hom.)
• Consequence: CSNK1A1L NM_145203.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.15
• Publications: 4 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.092393845).

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.13A>T	p.Ser5Cys	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.13A>T	p.Ser5Cys	missense	Exon 1 of 1	ENSP00000369126.3	Q8N752
	ENSG00000307674	ENST00000827784.1		n.212+508T>A		intron	N/A
	ENSG00000307674	ENST00000827785.1		n.195+508T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000154 AC: 23 AN: 149686 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000767

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000132

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000878 AC: 22 AN: 250498 AF XY: 0.0000960

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000465

Gnomad NFE exome AF: 0.000177

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000304 AC: 444 AN: 1458856 Hom.: 0 Cov.: 35 AF XY: 0.000296 AC XY: 215 AN XY: 725864

African (AFR) AF: 0.00 AC: 0 AN: 31608

American (AMR) AF: 0.00 AC: 0 AN: 44594

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26054

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

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86154

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53358

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.000380 AC: 422 AN: 1111460

Other (OTH) AF: 0.000316 AC: 19 AN: 60170

GnomAD4 genome AF: 0.000154 AC: 23 AN: 149686 Hom.: 0 Cov.: 33 AF XY: 0.000137 AC XY: 10 AN XY: 73154

African (AFR) AF: 0.0000767 AC: 3 AN: 39124

American (AMR) AF: 0.000132 AC: 2 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2068

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000159

ExAC AF: 0.0000994 AC: 12

EpiCase AF: 0.000109

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	13
DANN	Benign	0.72
DEOGEN2	Benign	0.045	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.1
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.092
Sift	Uncertain	0.027	D
Sift4G	Uncertain	0.032	D
Polyphen		0.0070	B
Vest4		0.21
MutPred		0.32		Gain of catalytic residue at K8 (P = 8e-04)
MVP		0.45
MPC		0.17
ClinPred		0.074	T
GERP RS		-1.0
PromoterAI		-0.033	Neutral
Varity_R		0.13
gMVP		0.57
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs56224973; hg19: chr13-37679381;