3-98007903-A-G

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001105580.3(GABRR3):​c.615T>C​(p.Tyr205Tyr) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000499 in 1,402,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: GABRR3 NM_001105580.3 splice_region, synonymous
• Scores: Splicing: ADA: 0.0002383
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.75

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

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BP7: Synonymous conserved (PhyloP=2.75 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRR3	NM_001105580.3	c.615T>C	p.Tyr205Tyr	splice_region_variant, synonymous_variant	Exon 7 of 10	ENST00000472788.6	NP_001099050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRR3	ENST00000472788.6	c.615T>C	p.Tyr205Tyr	splice_region_variant, synonymous_variant	Exon 7 of 10	5	NM_001105580.3	ENSP00000420790.1
GABRR3	ENST00000470589.1	n.501+4441T>C		intron_variant	Intron 5 of 5	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000499 AC: 7 AN: 1402950 Hom.: 0 Cov.: 32 AF XY: 0.00000577 AC XY: 4 AN XY: 692828

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000646

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	10

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00024
dbscSNV1_RF	Benign	0.064
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

Publications

LitVar

Other links and lift over

dbSNP: rs832032; hg19: chr3-97726747;