NM_033223.5:c.270+147969T>C

Variant names:

• chr15-27174790-T-C
• rs622959
• NM_033223.5:c.270+147969T>C

Variant summary

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

The NM_033223.5(GABRG3):​c.270+147969T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 152,018 control chromosomes in the GnomAD database, including 9,090 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 0.30 (9090 hom., cov: 32)
• Consequence: GABRG3 NM_033223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.272
• Publications: 0 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.547 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.270+147969T>C		intron	N/A	NP_150092.2
	GABRG3	NM_001270873.2		c.270+147969T>C		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.270+147969T>C		intron	N/A	ENSP00000479113.1
	GABRG3	ENST00000555083.5	TSL:2	c.270+147969T>C		intron	N/A	ENSP00000452244.1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46018 AN: 151900 Hom.: 9061 Cov.: 32

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.258

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

GnomAD4 genome AF: 0.303 AC: 46101 AN: 152018 Hom.: 9090 Cov.: 32 AF XY: 0.300 AC XY: 22307 AN XY: 74302

African (AFR) AF: 0.553 AC: 22893 AN: 41434

American (AMR) AF: 0.334 AC: 5104 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 478 AN: 3468

East Asian (EAS) AF: 0.285 AC: 1465 AN: 5138

South Asian (SAS) AF: 0.296 AC: 1424 AN: 4816

European-Finnish (FIN) AF: 0.186 AC: 1965 AN: 10588

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12048 AN: 67978

Other (OTH) AF: 0.259 AC: 546 AN: 2112

Alfa AF: 0.219 Hom.: 7813

Bravo AF: 0.326

Asia WGS AF: 0.341 AC: 1181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.2
DANN	Benign	0.45
PhyloP100		-0.27
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: rs622959; hg19: chr15-27419937;