5-123595128-G-A

Variant names:

• chr5-123595128-G-A
• rs141285750
• NM_001364140.2:c.1179G>A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6 BP7 BS2

The NM_001364140.2(CSNK1G3):​c.1179G>A​(p.Ser393Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0031 in 1,612,840 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0021 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (7 hom.)
• Consequence: CSNK1G3 NM_001364140.2 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.95

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 Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 5-123595128-G-A is Benign according to our data. Variant chr5-123595128-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3050578.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=1.95 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSNK1G3	NM_001364140.2	c.1179G>A	p.Ser393Ser	synonymous_variant	Exon 11 of 14	ENST00000696905.1	NP_001351069.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSNK1G3	ENST00000696905.1	c.1179G>A	p.Ser393Ser	synonymous_variant	Exon 11 of 14		NM_001364140.2	ENSP00000512966.1

Frequencies

GnomAD3 genomes AF: 0.00208 AC: 316 AN: 151928 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000798

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000590

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00381

Gnomad OTH AF: 0.00288

GnomAD3 exomes AF: 0.00175 AC: 438 AN: 250200 Hom.: 1 AF XY: 0.00175 AC XY: 236 AN XY: 135238

Gnomad AFR exome AF: 0.000617

Gnomad AMR exome AF: 0.000553

Gnomad ASJ exome AF: 0.00249

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000981

Gnomad FIN exome AF: 0.0000926

Gnomad NFE exome AF: 0.00320

Gnomad OTH exome AF: 0.00295

GnomAD4 exome AF: 0.00320 AC: 4677 AN: 1460794 Hom.: 7 Cov.: 30 AF XY: 0.00314 AC XY: 2284 AN XY: 726702

Gnomad4 AFR exome AF: 0.000569

Gnomad4 AMR exome AF: 0.000717

Gnomad4 ASJ exome AF: 0.00172

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000162

Gnomad4 FIN exome AF: 0.000244

Gnomad4 NFE exome AF: 0.00399

Gnomad4 OTH exome AF: 0.00192

GnomAD4 genome AF: 0.00208 AC: 316 AN: 152046 Hom.: 0 Cov.: 32 AF XY: 0.00160 AC XY: 119 AN XY: 74332

Gnomad4 AFR AF: 0.000796

Gnomad4 AMR AF: 0.000590

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.00381

Gnomad4 OTH AF: 0.00285

Alfa AF: 0.00270 Hom.: 1

Bravo AF: 0.00187

EpiCase AF: 0.00311

EpiControl AF: 0.00267

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

CSNK1G3-related disorder Benign:1

Aug 30, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	14
DANN	Benign	0.70

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: rs141285750; hg19: chr5-122930822;