Genetic Variant GABRG3:p.Thr321Thr (chr15-27527530-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

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. 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 0.49 ( 18885 hom., cov: 32)

Exomes 𝑓: 0.54 ( 212875 hom. )

Consequence

GABRG3
NM_033223.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.98

Variant links:

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]

GABRG3 links:

ENSG00000259168 (HGNC:):

ENSG00000259168 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRG3	NM_033223.5 link	c.963C>T	p.Thr321Thr	synonymous_variant	Exon 8 of 10	ENST00000615808.5	NP_150092.2	Q99928-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRG3	ENST00000615808.5 link	c.963C>T	p.Thr321Thr	synonymous_variant	Exon 8 of 10	1	NM_033223.5	ENSP00000479113.1		Q99928-1

Frequencies

GnomAD3 genomes

AF:

0.487

AC:

73984

AN:

151870

Hom.:

18877

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.551

AC:

137275

AN:

249092

Hom.:

39065

AF XY:

0.549

AC XY:

74218

AN XY:

135132

show subpopulations

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 SAS exome

AF:

0.542

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.:

AF XY:

0.537

AC XY:

390468

AN XY:

727080

show subpopulations

Gnomad4 AFR exome

AF:

0.318

Gnomad4 AMR exome

AF:

0.689

Gnomad4 ASJ exome

AF:

0.601

Gnomad4 EAS exome

AF:

0.697

Gnomad4 SAS exome

AF:

0.548

Gnomad4 FIN exome

AF:

0.504

Gnomad4 NFE exome

AF:

0.531

Gnomad4 OTH exome

AF:

0.524

GnomAD4 genome

AF:

0.487

AC:

74011

AN:

151988

Hom.:

18885

Cov.:

AF XY:

0.488

AC XY:

36265

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.327

Gnomad4 AMR

AF:

0.615

Gnomad4 ASJ

AF:

0.598

Gnomad4 EAS

AF:

0.650

Gnomad4 SAS

AF:

0.544

Gnomad4 FIN

AF:

0.516

Gnomad4 NFE

AF:

0.529

Gnomad4 OTH

AF:

0.525

Alfa

AF:

0.528

Hom.:

28838

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

3.4

DANN

Benign

0.94

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over