5-123604734-C-T

Variant names:

• chr5-123604734-C-T
• rs955530337
• NM_001364140.2:c.1196C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001364140.2(CSNK1G3):​c.1196C>T​(p.Ser399Phe) variant causes a missense change. 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)
• Consequence: CSNK1G3 NM_001364140.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.16

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37548175).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSNK1G3	NM_001364140.2	c.1196C>T	p.Ser399Phe	missense_variant	Exon 12 of 14	ENST00000696905.1	NP_001351069.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSNK1G3	ENST00000696905.1	c.1196C>T	p.Ser399Phe	missense_variant	Exon 12 of 14		NM_001364140.2	ENSP00000512966.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 22, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1193C>T (p.S398F) alteration is located in exon 12 (coding exon 11) of the CSNK1G3 gene. This alteration results from a C to T substitution at nucleotide position 1193, causing the serine (S) at amino acid position 398 to be replaced by a phenylalanine (F). 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	0.86
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	.;.;.;.;.;T;.
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.99	D;D;D;.;D;D;D
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.38	T;T;T;T;T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.8	.;.;.;.;.;L;L
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-4.2	D;D;D;D;D;D;D
REVEL	Benign	0.17
Sift	Uncertain	0.0030	D;D;D;D;D;D;D
Sift4G	Uncertain	0.041	D;D;D;D;D;T;T
Polyphen		0.044	B;.;.;B;.;B;B
Vest4		0.57
MutPred		0.34		.;.;.;.;.;Loss of disorder (P = 0.0034);Loss of disorder (P = 0.0034);
MVP		0.66
ClinPred		0.98	D
GERP RS		4.3
Varity_R		0.51
gMVP		0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs955530337; hg19: chr5-122940428;