NM_000811.3:c.1005C>G

Variant names:

• chr5-161692119-C-G
• rs13184586
• NM_000811.3:c.1005C>G

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_000811.3(GABRA6):​c.1005C>G​(p.Ala335Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 1,613,736 control chromosomes in the GnomAD database, including 236,907 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.48 (18132 hom., cov: 33)
  • Exomes 𝑓: 0.54 (218775 hom.)
• Consequence: GABRA6 NM_000811.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.318
• Publications: 22 publications found

Genes affected

GABRA6 (HGNC:4080): (gamma-aminobutyric acid type A receptor subunit alpha6) 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. At least 16 distinct subunits of GABA-A receptors have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 5-161692119-C-G is Benign according to our data. Variant chr5-161692119-C-G is described in ClinVar as Benign. ClinVar VariationId is 1169911.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.318 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRA6	NM_000811.3	c.1005C>G	p.Ala335Ala	synonymous_variant	Exon 8 of 9	ENST00000274545.10	NP_000802.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRA6	ENST00000274545.10	c.1005C>G	p.Ala335Ala	synonymous_variant	Exon 8 of 9	1	NM_000811.3	ENSP00000274545.5
GABRA6	ENST00000523217.5	c.975C>G	p.Ala325Ala	synonymous_variant	Exon 8 of 9	5		ENSP00000430527.1
GABRA6	ENST00000521520.1	n.998C>G		non_coding_transcript_exon_variant	Exon 2 of 3	2

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72734 AN: 151912 Hom.: 18131 Cov.: 33

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.454

GnomAD2 exomes AF: 0.481 AC: 121057 AN: 251464 AF XY: 0.488

Gnomad AFR exome AF: 0.360

Gnomad AMR exome AF: 0.343

Gnomad ASJ exome AF: 0.533

Gnomad EAS exome AF: 0.287

Gnomad FIN exome AF: 0.542

Gnomad NFE exome AF: 0.565

Gnomad OTH exome AF: 0.506

GnomAD4 exome AF: 0.542 AC: 792173 AN: 1461706 Hom.: 218775 Cov.: 50 AF XY: 0.540 AC XY: 392925 AN XY: 727170

African (AFR) AF: 0.362 AC: 12125 AN: 33476

American (AMR) AF: 0.351 AC: 15697 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 13985 AN: 26136

East Asian (EAS) AF: 0.311 AC: 12347 AN: 39694

South Asian (SAS) AF: 0.448 AC: 38652 AN: 86250

European-Finnish (FIN) AF: 0.544 AC: 29037 AN: 53420

Middle Eastern (MID) AF: 0.490 AC: 2829 AN: 5768

European-Non Finnish (NFE) AF: 0.572 AC: 635962 AN: 1111848

Other (OTH) AF: 0.522 AC: 31539 AN: 60390

GnomAD4 genome AF: 0.478 AC: 72744 AN: 152030 Hom.: 18132 Cov.: 33 AF XY: 0.476 AC XY: 35390 AN XY: 74288

African (AFR) AF: 0.360 AC: 14935 AN: 41472

American (AMR) AF: 0.427 AC: 6519 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 1824 AN: 3470

East Asian (EAS) AF: 0.304 AC: 1567 AN: 5156

South Asian (SAS) AF: 0.430 AC: 2067 AN: 4808

European-Finnish (FIN) AF: 0.553 AC: 5838 AN: 10564

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.567 AC: 38511 AN: 67972

Other (OTH) AF: 0.450 AC: 950 AN: 2110

Alfa AF: 0.457 Hom.: 2405

Bravo AF: 0.460

Asia WGS AF: 0.342 AC: 1191 AN: 3478

EpiCase AF: 0.559

EpiControl AF: 0.554

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Childhood absence epilepsy Benign:1

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

GABRA6-related disorder Benign:1

Oct 16, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.1
DANN	Benign	0.55
PhyloP100		0.32
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13184586; hg19: chr5-161119125; COSMIC: COSV50877703; COSMIC: COSV50877703;