chr15-27527530-C-T

Variant names:

• chr15-27527530-C-T
• rs140679
• NM_033223.5:c.963C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP7 BA1

The NM_033223.5(GABRG3):​c.963C>T​(p.Thr321Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 1,613,570 control chromosomes in the GnomAD database, including 231,760 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.49 (18885 hom., cov: 32)
  • Exomes 𝑓: 0.54 (212875 hom.)
• Consequence: GABRG3 NM_033223.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98
• Publications: 29 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 -9 ACMG points.

• BP7: Synonymous conserved (PhyloP=-1.98 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.632 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.963C>T	p.Thr321Thr	synonymous	Exon 8 of 10	NP_150092.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRG3	ENST00000615808.5	TSL:1 MANE Select	c.963C>T	p.Thr321Thr	synonymous	Exon 8 of 10	ENSP00000479113.1
	GABRG3	ENST00000333743.10	TSL:5	c.426C>T	p.Thr142Thr	synonymous	Exon 5 of 7	ENSP00000331912.7
	GABRG3	ENST00000451330.2	TSL:3	c.249C>T	p.Thr83Thr	synonymous	Exon 2 of 4	ENSP00000390708.2

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73984 AN: 151870 Hom.: 18877 Cov.: 32

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.529

Gnomad OTH AF: 0.525

GnomAD2 exomes AF: 0.551 AC: 137275 AN: 249092 AF XY: 0.549

Gnomad AFR exome AF: 0.320

Gnomad AMR exome AF: 0.700

Gnomad ASJ exome AF: 0.599

Gnomad EAS exome AF: 0.666

Gnomad FIN exome AF: 0.506

Gnomad NFE exome AF: 0.526

Gnomad OTH exome AF: 0.545

GnomAD4 exome AF: 0.536 AC: 783901 AN: 1461582 Hom.: 212875 Cov.: 58 AF XY: 0.537 AC XY: 390468 AN XY: 727080

African (AFR) AF: 0.318 AC: 10634 AN: 33480

American (AMR) AF: 0.689 AC: 30788 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.601 AC: 15705 AN: 26136

East Asian (EAS) AF: 0.697 AC: 27651 AN: 39698

South Asian (SAS) AF: 0.548 AC: 47256 AN: 86250

European-Finnish (FIN) AF: 0.504 AC: 26894 AN: 53394

Middle Eastern (MID) AF: 0.495 AC: 2853 AN: 5768

European-Non Finnish (NFE) AF: 0.531 AC: 590468 AN: 1111776

Other (OTH) AF: 0.524 AC: 31652 AN: 60370

GnomAD4 genome AF: 0.487 AC: 74011 AN: 151988 Hom.: 18885 Cov.: 32 AF XY: 0.488 AC XY: 36265 AN XY: 74270

African (AFR) AF: 0.327 AC: 13548 AN: 41418

American (AMR) AF: 0.615 AC: 9400 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 2075 AN: 3472

East Asian (EAS) AF: 0.650 AC: 3354 AN: 5160

South Asian (SAS) AF: 0.544 AC: 2616 AN: 4810

European-Finnish (FIN) AF: 0.516 AC: 5454 AN: 10564

Middle Eastern (MID) AF: 0.476 AC: 139 AN: 292

European-Non Finnish (NFE) AF: 0.529 AC: 35954 AN: 67964

Other (OTH) AF: 0.525 AC: 1108 AN: 2112

Alfa AF: 0.526 Hom.: 32988

Bravo AF: 0.490

Asia WGS AF: 0.539 AC: 1874 AN: 3478

EpiCase AF: 0.537

EpiControl AF: 0.541

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	3.4
DANN	Benign	0.94
PhyloP100		-2.0
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: rs140679; hg19: chr15-27772676;