NM_000796.6:c.383+774C>T

Variant names:

• chr3-114158981-G-A
• rs324032
• NM_000796.6:c.383+774C>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.383+774C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.874 in 151,820 control chromosomes in the GnomAD database, including 58,698 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 0.87 (58698 hom., cov: 28)
• Consequence: DRD3 NM_000796.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.339
• Publications: 4 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 = 0.934 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000796.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD3	NM_000796.6	MANE Select	c.383+774C>T		intron	N/A	NP_000787.2
	DRD3	NM_001282563.2		c.383+774C>T		intron	N/A	NP_001269492.1
	DRD3	NM_001290809.1		c.383+774C>T		intron	N/A	NP_001277738.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD3	ENST00000383673.5	TSL:1 MANE Select	c.383+774C>T		intron	N/A	ENSP00000373169.2
	DRD3	ENST00000467632.5	TSL:1	c.383+774C>T		intron	N/A	ENSP00000420662.1
	DRD3	ENST00000460779.5	TSL:2	c.383+774C>T		intron	N/A	ENSP00000419402.1

Frequencies

GnomAD3 genomes AF: 0.874 AC: 132572 AN: 151702 Hom.: 58690 Cov.: 28

Gnomad AFR AF: 0.717

Gnomad AMI AF: 0.859

Gnomad AMR AF: 0.899

Gnomad ASJ AF: 0.969

Gnomad EAS AF: 0.896

Gnomad SAS AF: 0.929

Gnomad FIN AF: 0.955

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.940

Gnomad OTH AF: 0.890

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

GnomAD4 genome AF: 0.874 AC: 132621 AN: 151820 Hom.: 58698 Cov.: 28 AF XY: 0.875 AC XY: 64948 AN XY: 74188

African (AFR) AF: 0.716 AC: 29580 AN: 41316

American (AMR) AF: 0.898 AC: 13705 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.969 AC: 3357 AN: 3466

East Asian (EAS) AF: 0.896 AC: 4594 AN: 5130

South Asian (SAS) AF: 0.930 AC: 4440 AN: 4774

European-Finnish (FIN) AF: 0.955 AC: 10108 AN: 10582

Middle Eastern (MID) AF: 0.887 AC: 259 AN: 292

European-Non Finnish (NFE) AF: 0.940 AC: 63925 AN: 67988

Other (OTH) AF: 0.888 AC: 1873 AN: 2110

Alfa AF: 0.901 Hom.: 7739

Bravo AF: 0.862

Asia WGS AF: 0.909 AC: 3161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.5
DANN	Benign	0.69
PhyloP100		0.34
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: rs324032; hg19: chr3-113877828;