NM_033223.5:c.713-5367G>A

Variant names:

• chr15-27514605-G-A
• rs8042799
• NM_033223.5:c.713-5367G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033223.5(GABRG3):​c.713-5367G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0732 in 152,164 control chromosomes in the GnomAD database, including 808 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 0.073 (808 hom., cov: 32)
• Consequence: GABRG3 NM_033223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.792
• Publications: 1 publications found

Genes affected

GABRG3 (HGNC:4088): (gamma-aminobutyric acid type A receptor subunit gamma3) This gene encodes a gamma-aminobutyric acid (GABA) receptor. GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA-A receptors, which are ligand-gated chloride channels. Chloride conductance of these channels can be modulated by agents such as benzodiazepines that bind to the GABA-A receptor. GABA-A receptors are pentameric, consisting of proteins from several subunit classes: alpha, beta, gamma, delta and rho. The protein encoded by this gene is a gamma subunit, which contains the benzodiazepine binding site. Two transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Aug 2012]

ENSG00000259168 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033223.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRG3	NM_033223.5	MANE Select	c.713-5367G>A		intron	N/A	NP_150092.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRG3	ENST00000615808.5	TSL:1 MANE Select	c.713-5367G>A		intron	N/A	ENSP00000479113.1
	GABRG3	ENST00000333743.10	TSL:5	c.176-5367G>A		intron	N/A	ENSP00000331912.7
	GABRG3	ENST00000554696.5	TSL:3	c.539-5367G>A		intron	N/A	ENSP00000451862.1

Frequencies

GnomAD3 genomes AF: 0.0730 AC: 11099 AN: 152046 Hom.: 802 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0396

Gnomad ASJ AF: 0.0861

Gnomad EAS AF: 0.0993

Gnomad SAS AF: 0.0332

Gnomad FIN AF: 0.0156

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0212

Gnomad OTH AF: 0.0733

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

GnomAD4 genome AF: 0.0732 AC: 11146 AN: 152164 Hom.: 808 Cov.: 32 AF XY: 0.0717 AC XY: 5336 AN XY: 74406

African (AFR) AF: 0.187 AC: 7763 AN: 41472

American (AMR) AF: 0.0398 AC: 609 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0861 AC: 299 AN: 3472

East Asian (EAS) AF: 0.0997 AC: 517 AN: 5186

South Asian (SAS) AF: 0.0328 AC: 158 AN: 4814

European-Finnish (FIN) AF: 0.0156 AC: 165 AN: 10598

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0212 AC: 1442 AN: 68002

Other (OTH) AF: 0.0731 AC: 154 AN: 2108

Alfa AF: 0.0356 Hom.: 303

Bravo AF: 0.0819

Asia WGS AF: 0.0880 AC: 307 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.7
DANN	Benign	0.65
PhyloP100		-0.79
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8042799; hg19: chr15-27759751;