Variant 5-123575736-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001364140.2(CSNK1G3):c.446G>A(p.Arg149His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,454,478 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

CSNK1G3
NM_001364140.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.89

Variant links:

Genes affected

CSNK1G3 (HGNC:2456): (casein kinase 1 gamma 3) This gene encodes a member of a family of serine/threonine protein kinases that phosphorylate caseins and other acidic proteins. A related protein in the African clawed frog participates in the transmission of Wnt/beta-catenin signaling. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]

CSNK1G3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.915

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSNK1G3	NM_001364140.2 linkuse as main transcript	c.446G>A	p.Arg149His	missense_variant	6/14	ENST00000696905.1	NP_001351069.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSNK1G3	ENST00000696905.1 linkuse as main transcript	c.446G>A	p.Arg149His	missense_variant	6/14		NM_001364140.2	ENSP00000512966.1		A0A8V8TKT3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

248676

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

134478

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:

0.0000335

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000886

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1454478

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

723708

show subpopulations

Gnomad4 AFR exome

AF:

0.0000302

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000903

Gnomad4 OTH exome

AF:

0.0000500

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.0000113

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Apr 01, 2024

The c.446G>A (p.R149H) alteration is located in exon 6 (coding exon 5) of the CSNK1G3 gene. This alteration results from a G to A substitution at nucleotide position 446, causing the arginine (R) at amino acid position 149 to be replaced by a histidine (H). 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

Pathogenic

0.93

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Pathogenic

0.19

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.24

.;.;.;.;.;T;.

Eigen

Pathogenic

0.95

Eigen_PC

Pathogenic

0.83

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

D;D;D;.;D;D;D

M_CAP

Uncertain

0.22

MetaRNN

Pathogenic

0.92

D;D;D;D;D;D;D

MetaSVM

Uncertain

0.44

MutationAssessor

Pathogenic

4.6

H;.;.;H;H;H;H

PrimateAI

Pathogenic

0.89

PROVEAN

Pathogenic

-4.7

D;D;D;D;D;D;D

REVEL

Pathogenic

0.69

Sift

Pathogenic

0.0

D;D;D;D;D;D;D

Sift4G

Uncertain

0.0030

D;D;D;D;D;D;D

Polyphen

1.0

D;.;.;D;.;D;D

Vest4

0.80

MutPred

0.78

Loss of MoRF binding (P = 0.0907);.;.;Loss of MoRF binding (P = 0.0907);Loss of MoRF binding (P = 0.0907);Loss of MoRF binding (P = 0.0907);Loss of MoRF binding (P = 0.0907);

MVP

0.77

ClinPred

1.0

GERP RS

4.0

Varity_R

0.93

gMVP

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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