chr5-123590505-G-A

Variant names:

• chr5-123590505-G-A
• rs1377474749
• NM_001364140.2:c.940G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001364140.2(CSNK1G3):​c.940G>A​(p.Asp314Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CSNK1G3 NM_001364140.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 10.0
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26160005).

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.940G>A	p.Asp314Asn	missense	Exon 9 of 14	NP_001351069.1	A0A8V8TKT3
	CSNK1G3	NM_001044723.3		c.937G>A	p.Asp313Asn	missense	Exon 9 of 14	NP_001038188.1
	CSNK1G3	NM_001437477.1		c.940G>A	p.Asp314Asn	missense	Exon 9 of 14	NP_001424406.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSNK1G3	ENST00000696905.1	MANE Select	c.940G>A	p.Asp314Asn	missense	Exon 9 of 14	ENSP00000512966.1	A0A8V8TKT3
	CSNK1G3	ENST00000345990.9	TSL:1	c.937G>A	p.Asp313Asn	missense	Exon 9 of 14	ENSP00000334735.5	Q9Y6M4-2
	CSNK1G3	ENST00000360683.6	TSL:1	c.937G>A	p.Asp313Asn	missense	Exon 8 of 13	ENSP00000353904.2	Q9Y6M4-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1390996 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 690858

African (AFR) AF: 0.00 AC: 0 AN: 29064

American (AMR) AF: 0.00 AC: 0 AN: 31810

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24564

East Asian (EAS) AF: 0.00 AC: 0 AN: 35108

South Asian (SAS) AF: 0.00 AC: 0 AN: 73088

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51922

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5578

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1082472

Other (OTH) AF: 0.00 AC: 0 AN: 57390

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.19
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Benign	0.092
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.49	N
PhyloP100		10
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.17
Sift	Benign	0.12	T
Sift4G	Benign	0.34	T
Polyphen		0.0010	B
Vest4		0.31
MutPred		0.36		Loss of helix (P = 0.0558)
MVP		0.53
ClinPred		0.95	D
GERP RS		4.8
Varity_R		0.41
gMVP		0.57
Mutation Taster		=47/53	disease causing

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: rs1377474749; hg19: chr5-122926199;