3-114139354-C-T

Position:

• chr3-114139354-C-T

Variant summary

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

The NM_000796.6(DRD3):​c.723+146G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 760,540 control chromosomes in the GnomAD database, including 25,568 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 0.21 (3969 hom., cov: 33)
  • Exomes 𝑓: 0.26 (21599 hom.)
• Consequence: DRD3 NM_000796.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.213

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 (EAS) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DRD3	NM_000796.6	c.723+146G>A		intron_variant		ENST00000383673.5
DRD3	NM_001282563.2	c.723+146G>A		intron_variant
DRD3	NM_001290809.1	c.723+146G>A		intron_variant
DRD3	NM_033663.6	c.723+146G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRD3	ENST00000383673.5	c.723+146G>A		intron_variant		1	NM_000796.6	P1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31661 AN: 152070 Hom.: 3971 Cov.: 33

Gnomad AFR AF: 0.0633

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.246

GnomAD4 exome AF: 0.261 AC: 158527 AN: 608352 Hom.: 21599 AF XY: 0.262 AC XY: 82222 AN XY: 313634

Gnomad4 AFR exome AF: 0.0589

Gnomad4 AMR exome AF: 0.217

Gnomad4 ASJ exome AF: 0.377

Gnomad4 EAS exome AF: 0.298

Gnomad4 SAS exome AF: 0.273

Gnomad4 FIN exome AF: 0.285

Gnomad4 NFE exome AF: 0.260

Gnomad4 OTH exome AF: 0.263

GnomAD4 genome AF: 0.208 AC: 31654 AN: 152188 Hom.: 3969 Cov.: 33 AF XY: 0.211 AC XY: 15673 AN XY: 74390

Gnomad4 AFR AF: 0.0631

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.372

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.244

Alfa AF: 0.240 Hom.: 2564

Bravo AF: 0.198

Asia WGS AF: 0.265 AC: 921 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	8.9
DANN	Benign	0.76

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: rs2134655; hg19: chr3-113858201;