NM_000811.3:c.305G>C

Variant names:

• chr5-161689028-G-C
• NM_000811.3:c.305G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000811.3(GABRA6):​c.305G>C​(p.Ser102Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GABRA6 NM_000811.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.03

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]

ENSG00000253403 (HGNC:40248):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRA6	NM_000811.3	c.305G>C	p.Ser102Thr	missense_variant	Exon 4 of 9	ENST00000274545.10	NP_000802.2
GABRA6-AS1	NR_189170.1	n.151+232C>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRA6	ENST00000274545.10	c.305G>C	p.Ser102Thr	missense_variant	Exon 4 of 9	1	NM_000811.3	ENSP00000274545.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Benign	0.91
DEOGEN2	Benign	0.077	T;.;.
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.72	T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.54	D;D;D
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.21	N;.;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	0.080	N;N;N
REVEL	Uncertain	0.39
Sift	Benign	1.0	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.26	B;.;.
Vest4		0.41
MutPred		0.55		Gain of phosphorylation at S102 (P = 0.0899);.;.;
MVP		0.84
MPC		0.23
ClinPred		0.89	D
GERP RS		5.7
Varity_R		0.28
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-161116034;