Variant 15-27520009-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_033223.5(GABRG3):c.750T>C(p.Ser250=) 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. In-silico tool predicts a benign outcome for this variant. 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0960

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 15-27520009-T-C is Benign according to our data. Variant chr15-27520009-T-C is described in ClinVar as [Benign]. Clinvar id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 23 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRG3	NM_033223.5 linkuse as main transcript	c.750T>C	p.Ser250=	synonymous_variant	7/10	ENST00000615808.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRG3	ENST00000615808.5 linkuse as main transcript	c.750T>C	p.Ser250=	synonymous_variant	7/10	1	NM_033223.5	P1	Q99928-1
	ENST00000556642.1 linkuse as main transcript	n.85+21104A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00876

AC:

1333

AN:

152168

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.00223

AC:

450

AN:

201960

Hom.:

AF XY:

0.00169

AC XY:

182

AN XY:

107754

show subpopulations

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 SAS 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.:

Cov.:

AF XY:

0.000739

AC XY:

522

AN XY:

706066

show subpopulations

Gnomad4 AFR exome

AF:

0.0310

Gnomad4 AMR exome

AF:

0.00113

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000494

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000165

Gnomad4 OTH exome

AF:

0.00186

GnomAD4 genome

AF:

0.00877

AC:

1335

AN:

152286

Hom.:

Cov.:

AF XY:

0.00810

AC XY:

603

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0309

Gnomad4 AMR

AF:

0.00222

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00371

Hom.:

Bravo

AF:

0.00966

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

6.3

DANN

Benign

0.80

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over