5-123545680-A-G

Position:

• chr5-123545680-A-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.17A>G​(p.Lys6Arg) 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. 14/21 in silico tools predict 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: 3.53

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 (HGNC:):

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=0.11738095).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSNK1G3	NM_001364140.2	c.17A>G	p.Lys6Arg	missense_variant	2/14	ENST00000696905.1	NP_001351069.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSNK1G3	ENST00000696905.1	c.17A>G	p.Lys6Arg	missense_variant	2/14		NM_001364140.2	ENSP00000512966.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 02, 2024

The c.17A>G (p.K6R) alteration is located in exon 2 (coding exon 1) of the CSNK1G3 gene. This alteration results from a A to G substitution at nucleotide position 17, causing the lysine (K) at amino acid position 6 to be replaced by an arginine (R). 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	0.070
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	21
DANN	Benign	0.82
DEOGEN2	Benign	0.073	.;.;.;T;.
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.00063
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.82	T;.;T;T;T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.12	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.38	N;N;N;N;N
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	0.18	N;N;N;N;N
REVEL	Benign	0.072
Sift	Benign	0.97	T;T;T;T;T
Sift4G	Benign	0.72	T;T;T;T;T
Polyphen		0.0010	B;B;.;B;B
Vest4		0.32
MutPred		0.22		Loss of methylation at K6 (P = 0.0109);Loss of methylation at K6 (P = 0.0109);Loss of methylation at K6 (P = 0.0109);Loss of methylation at K6 (P = 0.0109);Loss of methylation at K6 (P = 0.0109);
MVP		0.62
ClinPred		0.79	D
GERP RS		5.2
Varity_R		0.20
gMVP		0.64

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: chr5-122881374;