5-123591374-C-G

Variant names:

• chr5-123591374-C-G
• NM_001364140.2:c.1049C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001364140.2(CSNK1G3):​c.1049C>G​(p.Ala350Gly) variant causes a missense change involving the alteration of a non-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)
• Consequence: CSNK1G3 NM_001364140.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.14

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12793887).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSNK1G3	NM_001364140.2	c.1049C>G	p.Ala350Gly	missense_variant	Exon 10 of 14	ENST00000696905.1	NP_001351069.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSNK1G3	ENST00000696905.1	c.1049C>G	p.Ala350Gly	missense_variant	Exon 10 of 14		NM_001364140.2	ENSP00000512966.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 21, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1046C>G (p.A349G) alteration is located in exon 10 (coding exon 9) of the CSNK1G3 gene. This alteration results from a C to G substitution at nucleotide position 1046, causing the alanine (A) at amino acid position 349 to be replaced by a glycine (G). 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	Benign	0.074
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	.;.;.;.;.;T;.
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.95	D;D;D;.;D;D;D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.13	T;T;T;T;T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	0.69	N;.;.;N;.;N;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.76	N;N;N;N;N;N;N
REVEL	Benign	0.062
Sift	Benign	0.33	T;T;T;T;T;T;T
Sift4G	Benign	0.43	T;T;T;T;T;T;T
Polyphen		0.053	B;.;.;B;.;B;B
Vest4		0.21
MutPred		0.18		Loss of stability (P = 0.0274);.;.;Loss of stability (P = 0.0274);.;Loss of stability (P = 0.0274);Loss of stability (P = 0.0274);
MVP		0.34
ClinPred		0.37	T
GERP RS		4.1
Varity_R		0.099
gMVP		0.18

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-122927068;