rs9828046

chr3-114139416-G-Achr3-114139416-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000796.6(DRD3):c.723+84C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0299 in 1,334,702 control chromosomes in the GnomAD database, including 900 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.047 (259 hom., cov: 33)
  • Exomes 𝑓: 0.028 (641 hom.)
• Consequence: DRD3 NM_000796.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.56

Genes affected

DRD3 (HGNC:3024): (dopamine receptor D3) This gene encodes the D3 subtype of the five (D1-D5) dopamine receptors. The activity of the D3 subtype receptor is mediated by G proteins which inhibit adenylyl cyclase. This receptor is localized to the limbic areas of the brain, which are associated with cognitive, emotional, and endocrine functions. Genetic variation in this gene may be associated with susceptibility to hereditary essential tremor 1. Alternative splicing of this gene results in transcript variants encoding different isoforms, although some variants may be subject to nonsense-mediated decay (NMD). [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DRD3	NM_000796.6	c.723+84C>T		intron_variant		ENST00000383673.5
DRD3	NM_001282563.2	c.723+84C>T		intron_variant
DRD3	NM_001290809.1	c.723+84C>T		intron_variant
DRD3	NM_033663.6	c.723+84C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRD3	ENST00000383673.5	c.723+84C>T		intron_variant		1	NM_000796.6	P1

Frequencies

GnomAD3 genomes AF: 0.0468 AC: 7123 AN: 152128 Hom.: 259 Cov.: 33

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0235

Gnomad ASJ AF: 0.0110

Gnomad EAS AF: 0.00366

Gnomad SAS AF: 0.0468

Gnomad FIN AF: 0.0209

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0269

Gnomad OTH AF: 0.0372

GnomAD4 exome AF: 0.0277 AC: 32757 AN: 1182456 Hom.: 641 AF XY: 0.0280 AC XY: 16293 AN XY: 582252

Gnomad4 AFR exome AF: 0.105

Gnomad4 AMR exome AF: 0.0168

Gnomad4 ASJ exome AF: 0.0104

Gnomad4 EAS exome AF: 0.00263

Gnomad4 SAS exome AF: 0.0492

Gnomad4 FIN exome AF: 0.0227

Gnomad4 NFE exome AF: 0.0259

Gnomad4 OTH exome AF: 0.0298

GnomAD4 genome AF: 0.0469 AC: 7146 AN: 152246 Hom.: 259 Cov.: 33 AF XY: 0.0465 AC XY: 3464 AN XY: 74458

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.0234

Gnomad4 ASJ AF: 0.0110

Gnomad4 EAS AF: 0.00366

Gnomad4 SAS AF: 0.0466

Gnomad4 FIN AF: 0.0209

Gnomad4 NFE AF: 0.0270

Gnomad4 OTH AF: 0.0369

Alfa AF: 0.0298 Hom.: 79

Bravo AF: 0.0487

Asia WGS AF: 0.0280 AC: 98 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	9.8
Dann	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs9828046; hg19: chr3-113858263;