rs3773678

Variant names:

• chr3-114151231-A-G
• rs3773678
• NM_000796.6:c.384-3674T>C

Your query was ambiguous. Multiple possible variants found:

• chr3-114151231-A-G
• chr3-114151231-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000796.6(DRD3):​c.384-3674T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 152,102 control chromosomes in the GnomAD database, including 43,878 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 0.73 (43878 hom., cov: 31)
• Consequence: DRD3 NM_000796.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.392
• Publications: 31 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD3	NM_000796.6	c.384-3674T>C		intron_variant	Intron 3 of 6	ENST00000383673.5	NP_000787.2
DRD3	NM_001282563.2	c.384-3674T>C		intron_variant	Intron 4 of 7		NP_001269492.1
DRD3	NM_001290809.1	c.384-3674T>C		intron_variant	Intron 4 of 7		NP_001277738.1
DRD3	NM_033663.6	c.384-3674T>C		intron_variant	Intron 3 of 7		NP_387512.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRD3	ENST00000383673.5	c.384-3674T>C		intron_variant	Intron 3 of 6	1	NM_000796.6	ENSP00000373169.2

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110575 AN: 151984 Hom.: 43878 Cov.: 31

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.831

Gnomad AMR AF: 0.804

Gnomad ASJ AF: 0.841

Gnomad EAS AF: 0.839

Gnomad SAS AF: 0.747

Gnomad FIN AF: 0.926

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.874

Gnomad OTH AF: 0.757

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.727 AC: 110596 AN: 152102 Hom.: 43878 Cov.: 31 AF XY: 0.730 AC XY: 54287 AN XY: 74360

African (AFR) AF: 0.378 AC: 15684 AN: 41450

American (AMR) AF: 0.804 AC: 12279 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.841 AC: 2915 AN: 3468

East Asian (EAS) AF: 0.839 AC: 4327 AN: 5160

South Asian (SAS) AF: 0.748 AC: 3602 AN: 4818

European-Finnish (FIN) AF: 0.926 AC: 9820 AN: 10610

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.874 AC: 59412 AN: 68002

Other (OTH) AF: 0.754 AC: 1590 AN: 2108

Alfa AF: 0.832 Hom.: 227428

Bravo AF: 0.704

Asia WGS AF: 0.764 AC: 2658 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.8
DANN	Benign	0.35
PhyloP100		0.39
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3773678; hg19: chr3-113870078;