NM_033223.5:c.575-13152G>A

Variant names:

• chr15-27467498-G-A
• rs74006954
• NM_033223.5:c.575-13152G>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.575-13152G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.099 in 152,266 control chromosomes in the GnomAD database, including 1,342 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 0.099 (1342 hom., cov: 33)
• Consequence: GABRG3 NM_033223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.736
• Publications: 6 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.234 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.575-13152G>A		intron	N/A	NP_150092.2
	GABRG3	NM_001270873.2		c.575-13152G>A		intron	N/A	NP_001257802.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRG3	ENST00000615808.5	TSL:1 MANE Select	c.575-13152G>A		intron	N/A	ENSP00000479113.1
	GABRG3	ENST00000333743.10	TSL:5	c.38-13152G>A		intron	N/A	ENSP00000331912.7
	GABRG3	ENST00000554696.5	TSL:3	c.401-13152G>A		intron	N/A	ENSP00000451862.1

Frequencies

GnomAD3 genomes AF: 0.0990 AC: 15064 AN: 152148 Hom.: 1342 Cov.: 33

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.0433

Gnomad ASJ AF: 0.0280

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.0508

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0347

Gnomad OTH AF: 0.0635

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

GnomAD4 genome AF: 0.0990 AC: 15080 AN: 152266 Hom.: 1342 Cov.: 33 AF XY: 0.0981 AC XY: 7300 AN XY: 74446

African (AFR) AF: 0.238 AC: 9871 AN: 41530

American (AMR) AF: 0.0431 AC: 659 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0280 AC: 97 AN: 3470

East Asian (EAS) AF: 0.158 AC: 817 AN: 5172

South Asian (SAS) AF: 0.109 AC: 525 AN: 4826

European-Finnish (FIN) AF: 0.0508 AC: 539 AN: 10610

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0347 AC: 2362 AN: 68030

Other (OTH) AF: 0.0619 AC: 131 AN: 2116

Alfa AF: 0.0622 Hom.: 1072

Bravo AF: 0.103

Asia WGS AF: 0.145 AC: 501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.19
DANN	Benign	0.62
PhyloP100		-0.74
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: rs74006954; hg19: chr15-27712644;