rs34130136

Variant names:

• chr15-27520009-T-C
• rs34130136
• NM_033223.5:c.750T>C

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP6_Very_Strong BP7 BS1 BS2

The NM_033223.5(GABRG3):​c.750T>C​(p.Ser250Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00162 in 1,578,080 control chromosomes in the GnomAD database, including 36 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0088 (23 hom., cov: 32)
  • Exomes 𝑓: 0.00085 (13 hom.)
• Consequence: GABRG3 NM_033223.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0960
• 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 -17 ACMG points.

• BP6: Variant 15-27520009-T-C is Benign according to our data. Variant chr15-27520009-T-C is described in ClinVar as Benign. ClinVar VariationId is 787957.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.096 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00877 (1335/152286) while in subpopulation AFR AF = 0.0309 (1283/41556). AF 95% confidence interval is 0.0295. There are 23 homozygotes in GnomAd4. There are 603 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 23 gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRG3	NM_033223.5	MANE Select	c.750T>C	p.Ser250Ser	synonymous	Exon 7 of 10	NP_150092.2	Q99928-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRG3	ENST00000615808.5	TSL:1 MANE Select	c.750T>C	p.Ser250Ser	synonymous	Exon 7 of 10	ENSP00000479113.1	Q99928-1
	GABRG3	ENST00000333743.10	TSL:5	c.213T>C	p.Ser71Ser	synonymous	Exon 4 of 7	ENSP00000331912.7	A0A0A0MR73
	GABRG3	ENST00000554696.5	TSL:3	c.576T>C	p.Ser192Ser	synonymous	Exon 5 of 6	ENSP00000451862.1	H0YJP1

Frequencies

GnomAD3 genomes AF: 0.00876 AC: 1333 AN: 152168 Hom.: 23 Cov.: 32

Gnomad AFR AF: 0.0309

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00223

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00527

GnomAD2 exomes AF: 0.00223 AC: 450 AN: 201960 AF XY: 0.00169

Gnomad AFR exome AF: 0.0326

Gnomad AMR exome AF: 0.000711

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000690

Gnomad OTH exome AF: 0.000192

GnomAD4 exome AF: 0.000851 AC: 1214 AN: 1425794 Hom.: 13 Cov.: 29 AF XY: 0.000739 AC XY: 522 AN XY: 706066

African (AFR) AF: 0.0310 AC: 1025 AN: 33028

American (AMR) AF: 0.00113 AC: 44 AN: 39038

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25560

East Asian (EAS) AF: 0.00 AC: 0 AN: 39090

South Asian (SAS) AF: 0.0000494 AC: 4 AN: 81030

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51808

Middle Eastern (MID) AF: 0.00227 AC: 13 AN: 5720

European-Non Finnish (NFE) AF: 0.0000165 AC: 18 AN: 1091398

Other (OTH) AF: 0.00186 AC: 110 AN: 59122

GnomAD4 genome AF: 0.00877 AC: 1335 AN: 152286 Hom.: 23 Cov.: 32 AF XY: 0.00810 AC XY: 603 AN XY: 74458

African (AFR) AF: 0.0309 AC: 1283 AN: 41556

American (AMR) AF: 0.00222 AC: 34 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68016

Other (OTH) AF: 0.00521 AC: 11 AN: 2110

Alfa AF: 0.00385 Hom.: 3

Bravo AF: 0.00966

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	6.3
DANN	Benign	0.80
PhyloP100		-0.096
PromoterAI		0.0086	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs34130136; hg19: chr15-27765155;