3-98007903-A-T

Variant names:

• chr3-98007903-A-T
• rs832032
• NM_001105580.3:c.615T>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001105580.3(GABRR3):​c.615T>A​(p.Tyr205*) variant causes a stop gained, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 1,554,836 control chromosomes in the GnomAD database, including 32,408 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely risk allele (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.21 (3692 hom., cov: 32)
  • Exomes 𝑓: 0.20 (28716 hom.)
• Consequence: GABRR3 NM_001105580.3 stop_gained, splice_region
• Clinical Significance: Likely risk allele no assertion criteria provided P:1
• Conservation: PhyloP100: 2.75
• Publications: 34 publications found

Genes affected

GABRR3 (HGNC:17969): (gamma-aminobutyric acid type A receptor subunit rho3) The neurotransmitter gamma-aminobutyric acid (GABA) functions in the central nervous system to regulate synaptic transmission of neurons. This gene encodes one of three related subunits, which combine as homo- or hetero-pentamers to form GABA(C) receptors. In humans, some individuals contain a single-base polymorphism (dbSNP rs832032) that is predicted to inactivate the gene product. [provided by RefSeq, Jan 2012]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001105580.3. 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
	GABRR3	NM_001105580.3	MANE Select	c.615T>A	p.Tyr205*	stop_gained splice_region	Exon 7 of 10	NP_001099050.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRR3	ENST00000472788.6	TSL:5 MANE Select	c.615T>A	p.Tyr205*	stop_gained splice_region	Exon 7 of 10	ENSP00000420790.1
	GABRR3	ENST00000470589.1	TSL:1	n.501+4441T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32178 AN: 152034 Hom.: 3686 Cov.: 32

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.0104

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.214

GnomAD4 exome AF: 0.197 AC: 276501 AN: 1402684 Hom.: 28716 Cov.: 32 AF XY: 0.198 AC XY: 136892 AN XY: 692680

African (AFR) AF: 0.285 AC: 8990 AN: 31540

American (AMR) AF: 0.128 AC: 4281 AN: 33546

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 5465 AN: 24830

East Asian (EAS) AF: 0.00599 AC: 225 AN: 37588

South Asian (SAS) AF: 0.210 AC: 16350 AN: 77688

European-Finnish (FIN) AF: 0.156 AC: 7905 AN: 50626

Middle Eastern (MID) AF: 0.267 AC: 1511 AN: 5660

European-Non Finnish (NFE) AF: 0.203 AC: 220348 AN: 1082964

Other (OTH) AF: 0.196 AC: 11426 AN: 58242

GnomAD4 genome AF: 0.212 AC: 32213 AN: 152152 Hom.: 3692 Cov.: 32 AF XY: 0.207 AC XY: 15370 AN XY: 74404

African (AFR) AF: 0.276 AC: 11457 AN: 41482

American (AMR) AF: 0.180 AC: 2751 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 742 AN: 3462

East Asian (EAS) AF: 0.0106 AC: 55 AN: 5182

South Asian (SAS) AF: 0.195 AC: 941 AN: 4828

European-Finnish (FIN) AF: 0.152 AC: 1614 AN: 10602

Middle Eastern (MID) AF: 0.295 AC: 86 AN: 292

European-Non Finnish (NFE) AF: 0.206 AC: 14027 AN: 67988

Other (OTH) AF: 0.212 AC: 448 AN: 2112

Alfa AF: 0.204 Hom.: 2539

Bravo AF: 0.216

ClinVar

ClinVar submissions as Germline

Significance: Likely risk allele

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Restless legs (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	37
PhyloP100		2.7
Vest4		0.35

Splicing

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

Other links and lift over

dbSNP: rs832032; hg19: chr3-97726747;