16-24292253-C-T

Position:

• chr16-24292253-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_006539.4(CACNG3):​c.211+35288C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,038 control chromosomes in the GnomAD database, including 3,461 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.20 (3461 hom., cov: 32)
• Consequence: CACNG3 NM_006539.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.416

Genes affected

CACNG3 (HGNC:1407): (calcium voltage-gated channel auxiliary subunit gamma 3) The protein encoded by this gene is a type I transmembrane AMPA receptor regulatory protein (TARP). TARPs regulate both trafficking and channel gating of the AMPA receptors. This gene is part of a functionally diverse eight-member protein subfamily of the PMP-22/EMP/MP20 family. This gene is a susceptibility locus for childhood absence epilepsy. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNG3	NM_006539.4	c.211+35288C>T		intron_variant		ENST00000005284.4	NP_006530.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNG3	ENST00000005284.4	c.211+35288C>T		intron_variant		1	NM_006539.4	ENSP00000005284.4

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30301 AN: 151918 Hom.: 3459 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.194

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.199 AC: 30312 AN: 152038 Hom.: 3461 Cov.: 32 AF XY: 0.195 AC XY: 14513 AN XY: 74308

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.123

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.273

Gnomad4 OTH AF: 0.195

Alfa AF: 0.240 Hom.: 5986

Bravo AF: 0.190

Asia WGS AF: 0.145 AC: 502 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	16
DANN	Benign	0.85

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: rs11640935; hg19: chr16-24303574;