Variant 13-37105244-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S5G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00030 ( 0 hom. )

Consequence

CSNK1A1L
NM_145203.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.15

Variant links:

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]

CSNK1A1L links:

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ACMG classification

Classification made for transcript

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=0.092393845).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSNK1A1L	NM_145203.6 linkuse as main transcript	c.13A>T	p.Ser5Cys	missense_variant	1/1	ENST00000379800.4	NP_660204.2	Q8N752

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSNK1A1L	ENST00000379800.4 linkuse as main transcript	c.13A>T	p.Ser5Cys	missense_variant	1/1	6	NM_145203.6	ENSP00000369126.3		Q8N752

Frequencies

GnomAD3 genomes

AF:

0.000154

AC:

AN:

149686

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0000878

AC:

AN:

250498

Hom.:

AF XY:

0.0000960

AC XY:

AN XY:

135376

show subpopulations

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 SAS 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.:

Cov.:

AF XY:

0.000296

AC XY:

215

AN XY:

725864

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000380

Gnomad4 OTH exome

AF:

0.000316

GnomAD4 genome

AF:

0.000154

AC:

AN:

149686

Hom.:

Cov.:

AF XY:

0.000137

AC XY:

AN XY:

73154

show subpopulations

Gnomad4 AFR

AF:

0.0000767

Gnomad4 AMR

AF:

0.000132

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000159

ExAC

AF:

0.0000994

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000415

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 18, 2023

The c.13A>T (p.S5C) alteration is located in exon 1 (coding exon 1) of the CSNK1A1L gene. This alteration results from a A to T substitution at nucleotide position 13, causing the serine (S) at amino acid position 5 to be replaced by a cysteine (C). 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

0.080

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.72

DEOGEN2

Benign

0.045

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.32

M_CAP

Benign

0.0046

MetaRNN

Benign

0.092

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

MutationTaster

Benign

0.93

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.3

REVEL

Benign

0.092

Sift

Uncertain

0.027

Sift4G

Uncertain

0.032

Polyphen

0.0070

Vest4

0.21

MutPred

0.32

Gain of catalytic residue at K8 (P = 8e-04);

MVP

0.45

MPC

0.17

ClinPred

0.074

GERP RS

-1.0

Varity_R

0.13

gMVP

0.57

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over