rs955032767

Variant names:

• chr5-123573501-C-T
• rs955032767
• NM_001364140.2:c.398C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001364140.2(CSNK1G3):​c.398C>T​(p.Thr133Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,364 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: CSNK1G3 NM_001364140.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.04
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.408554).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364140.2. 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
	CSNK1G3	NM_001364140.2	MANE Select	c.398C>T	p.Thr133Ile	missense	Exon 5 of 14	NP_001351069.1	A0A8V8TKT3
	CSNK1G3	NM_001044723.3		c.398C>T	p.Thr133Ile	missense	Exon 5 of 14	NP_001038188.1
	CSNK1G3	NM_001437477.1		c.398C>T	p.Thr133Ile	missense	Exon 5 of 14	NP_001424406.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSNK1G3	ENST00000696905.1	MANE Select	c.398C>T	p.Thr133Ile	missense	Exon 5 of 14	ENSP00000512966.1	A0A8V8TKT3
	CSNK1G3	ENST00000345990.9	TSL:1	c.398C>T	p.Thr133Ile	missense	Exon 5 of 14	ENSP00000334735.5	Q9Y6M4-2
	CSNK1G3	ENST00000360683.6	TSL:1	c.398C>T	p.Thr133Ile	missense	Exon 4 of 13	ENSP00000353904.2	Q9Y6M4-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461364 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726946

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 86102

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111822

Other (OTH) AF: 0.00 AC: 0 AN: 60368

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000468 Hom.: 0

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	0.24
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		5.0
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.30
Sift	Benign	0.042	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.99	D
Vest4		0.49
MutPred		0.41		Gain of ubiquitination at K137 (P = 0.0828)
MVP		0.31
ClinPred		0.99	D
GERP RS		4.3
Varity_R		0.44
gMVP		0.64
Mutation Taster		=60/40	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: rs955032767; hg19: chr5-122909195;