NM_000796.6:c.384-1458C>G

Variant names:

• chr3-114149015-G-C
• rs324036
• NM_000796.6:c.384-1458C>G

Variant summary

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

The NM_000796.6(DRD3):​c.384-1458C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 152,152 control chromosomes in the GnomAD database, including 43,822 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 (43822 hom., cov: 32)
• Consequence: DRD3 NM_000796.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.272
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD3	NM_000796.6	c.384-1458C>G		intron_variant	Intron 3 of 6	ENST00000383673.5	NP_000787.2
DRD3	NM_001282563.2	c.384-1458C>G		intron_variant	Intron 4 of 7		NP_001269492.1
DRD3	NM_001290809.1	c.384-1458C>G		intron_variant	Intron 4 of 7		NP_001277738.1
DRD3	NM_033663.6	c.384-1458C>G		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.384-1458C>G		intron_variant	Intron 3 of 6	1	NM_000796.6	ENSP00000373169.2

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110467 AN: 152032 Hom.: 43821 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.833

Gnomad AMR AF: 0.803

Gnomad ASJ AF: 0.841

Gnomad EAS AF: 0.839

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.925

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.873

Gnomad OTH AF: 0.755

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

GnomAD4 genome AF: 0.726 AC: 110490 AN: 152152 Hom.: 43822 Cov.: 32 AF XY: 0.729 AC XY: 54225 AN XY: 74376

African (AFR) AF: 0.376 AC: 15561 AN: 41438

American (AMR) AF: 0.803 AC: 12294 AN: 15302

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

East Asian (EAS) AF: 0.839 AC: 4342 AN: 5174

South Asian (SAS) AF: 0.747 AC: 3600 AN: 4818

European-Finnish (FIN) AF: 0.925 AC: 9826 AN: 10618

Middle Eastern (MID) AF: 0.717 AC: 208 AN: 290

European-Non Finnish (NFE) AF: 0.873 AC: 59399 AN: 68024

Other (OTH) AF: 0.752 AC: 1587 AN: 2110

Alfa AF: 0.729 Hom.: 2691

Bravo AF: 0.703

Asia WGS AF: 0.764 AC: 2656 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.51
PhyloP100		0.27
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: rs324036; hg19: chr3-113867862;