Genetic Variant NM_145203.6:c.13A>T (chr13-37105244-T-A) – ACMG Classification: Likely_benign (-2 pts)

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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.15

Publications

4 publications found

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:

ENSG00000307674 (HGNC:):

ENSG00000307674 links:

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ACMG classification

Classification was made for transcript

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

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:

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

GnomAD2 exomes

AF:

0.0000878

AC:

AN:

250498

AF XY:

0.0000960

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 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

African (AFR)

AF:

0.00

AC:

AN:

31608

American (AMR)

AF:

0.00

AC:

AN:

44594

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26054

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86154

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53358

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.000380

AC:

422

AN:

1111460

Other (OTH)

AF:

0.000316

AC:

AN:

60170

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

112

140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000154

AC:

AN:

149686

Hom.:

Cov.:

AF XY:

0.000137

AC XY:

AN XY:

73154

show subpopulations

African (AFR)

AF:

0.0000767

AC:

AN:

39124

American (AMR)

AF:

0.000132

AC:

AN:

15186

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000265

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000159

ExAC

AF:

0.0000994

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000415

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

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

PhyloP100

2.1

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

PromoterAI

-0.033

Neutral

(source)

Varity_R

0.13

gMVP

0.57

Mutation Taster

=83/17

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over