5-161688997-T-C

Variant names:

• chr5-161688997-T-C
• NM_000811.3:c.274T>C
• GABRA6 p.Leu92Leu

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_000811.3(GABRA6):​c.274T>C​(p.Leu92Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L92L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GABRA6 NM_000811.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.255
• Publications: 0 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]

GABRA6-AS1 (HGNC:40248):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP7: Synonymous conserved (PhyloP=0.255 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000811.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRA6	NM_000811.3	MANE Select	c.274T>C	p.Leu92Leu	synonymous	Exon 4 of 9	NP_000802.2	Q16445
	GABRA6-AS1	NR_189170.1		n.151+263A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRA6	ENST00000274545.10	TSL:1 MANE Select	c.274T>C	p.Leu92Leu	synonymous	Exon 4 of 9	ENSP00000274545.5	Q16445
	GABRA6	ENST00000523217.5	TSL:5	c.244T>C	p.Leu82Leu	synonymous	Exon 4 of 9	ENSP00000430527.1	E7EV53
	GABRA6	ENST00000520000.5	TSL:4	c.91T>C	p.Leu31Leu	synonymous	Exon 2 of 5	ENSP00000429943.1	H0YBP3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	10
DANN	Benign	0.73
PhyloP100		0.26
PromoterAI		0.0024	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-161116003;