Genetic Variant GABRG3:p.Thr321Thr (chr15-27527530-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP7BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.98

Publications

29 publications found

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 was made for transcript

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.

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

GnomAD2 exomes

AF:

0.551

AC:

137275

AN:

249092

AF XY:

0.549

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 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

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

19737

39474

59210

78947

98684

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16908

33816

50724

67632

84540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.487

AC:

74011

AN:

151988

Hom.:

18885

Cov.:

AF XY:

0.488

AC XY:

36265

AN XY:

74270

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1877

3754

5631

7508

9385

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

674

1348

2022

2696

3370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

3.4

(source)

DANN

Benign

0.94

PhyloP100

-2.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over