chr15-27527530-C-A

Variant names:

• chr15-27527530-C-A
• rs140679
• NM_033223.5:c.963C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP7

The NM_033223.5(GABRG3):​c.963C>A​(p.Thr321Thr) variant causes a synonymous change involving the alteration of a non-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: GABRG3 NM_033223.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98
• Publications: 29 publications found

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]

ENSG00000259168 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP7: Synonymous conserved (PhyloP=-1.98 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033223.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRG3	NM_033223.5	MANE Select	c.963C>A	p.Thr321Thr	synonymous	Exon 8 of 10	NP_150092.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRG3	ENST00000615808.5	TSL:1 MANE Select	c.963C>A	p.Thr321Thr	synonymous	Exon 8 of 10	ENSP00000479113.1
	GABRG3	ENST00000333743.10	TSL:5	c.426C>A	p.Thr142Thr	synonymous	Exon 5 of 7	ENSP00000331912.7
	GABRG3	ENST00000451330.2	TSL:3	c.249C>A	p.Thr83Thr	synonymous	Exon 2 of 4	ENSP00000390708.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 58

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	2.1
DANN	Benign	0.91
PhyloP100		-2.0

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

Other links and lift over

dbSNP: rs140679; hg19: chr15-27772676;