5-123553121-A-T

Variant names:

• chr5-123553121-A-T
• NM_001364140.2:c.193A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001364140.2(CSNK1G3):​c.193A>T​(p.Thr65Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CSNK1G3 NM_001364140.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.67
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.193A>T	p.Thr65Ser	missense	Exon 3 of 14	NP_001351069.1	A0A8V8TKT3
	CSNK1G3	NM_001044723.3		c.193A>T	p.Thr65Ser	missense	Exon 3 of 14	NP_001038188.1
	CSNK1G3	NM_001437477.1		c.193A>T	p.Thr65Ser	missense	Exon 3 of 14	NP_001424406.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSNK1G3	ENST00000696905.1	MANE Select	c.193A>T	p.Thr65Ser	missense	Exon 3 of 14	ENSP00000512966.1	A0A8V8TKT3
	CSNK1G3	ENST00000345990.9	TSL:1	c.193A>T	p.Thr65Ser	missense	Exon 3 of 14	ENSP00000334735.5	Q9Y6M4-2
	CSNK1G3	ENST00000360683.6	TSL:1	c.193A>T	p.Thr65Ser	missense	Exon 2 of 13	ENSP00000353904.2	Q9Y6M4-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 21

GnomAD4 genome Cov.: 32

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	0.31
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.10	T
Eigen	Benign	0.0017
Eigen_PC	Benign	0.18
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		7.7
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.11
Sift	Benign	0.18	T
Sift4G	Benign	0.30	T
Polyphen		0.034	B
Vest4		0.66
MutPred		0.49		Loss of catalytic residue at T65 (P = 0.0681)
MVP		0.48
ClinPred		0.89	D
GERP RS		4.8
Varity_R		0.30
gMVP		0.25
Mutation Taster		=64/36	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

hg19: chr5-122888815;