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GeneBe

15-27520009-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

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

2

Clinical Significance

Benign criteria provided, single submitter B:1

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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.096 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
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
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 23 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GABRG3NM_033223.5 linkuse as main transcriptc.750T>C p.Ser250= synonymous_variant 7/10 ENST00000615808.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GABRG3ENST00000615808.5 linkuse as main transcriptc.750T>C p.Ser250= synonymous_variant 7/101 NM_033223.5 P1Q99928-1
ENST00000556642.1 linkuse as main transcriptn.85+21104A>G intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00876
AC:
1333
AN:
152168
Hom.:
23
Cov.:
32
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.:
5
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.:
13
Cov.:
29
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00877
AC:
1335
AN:
152286
Hom.:
23
Cov.:
32
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.:
3
Bravo
AF:
0.00966
Asia WGS
AF:
0.00144
AC:
5
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 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.

Other links and lift over

dbSNP: rs34130136; hg19: chr15-27765155; API