3-114150007-A-C

Variant names:

• chr3-114150007-A-C
• rs324035
• NM_000796.6:c.384-2450T>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.384-2450T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 152,130 control chromosomes in the GnomAD database, including 36,350 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 0.65 (36350 hom., cov: 32)
• Consequence: DRD3 NM_000796.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.608
• Publications: 15 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD3	NM_000796.6	c.384-2450T>G		intron_variant	Intron 3 of 6	ENST00000383673.5	NP_000787.2
DRD3	NM_001282563.2	c.384-2450T>G		intron_variant	Intron 4 of 7		NP_001269492.1
DRD3	NM_001290809.1	c.384-2450T>G		intron_variant	Intron 4 of 7		NP_001277738.1
DRD3	NM_033663.6	c.384-2450T>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.384-2450T>G		intron_variant	Intron 3 of 6	1	NM_000796.6	ENSP00000373169.2

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98635 AN: 152012 Hom.: 36353 Cov.: 32

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.816

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.782

Gnomad EAS AF: 0.830

Gnomad SAS AF: 0.638

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.816

Gnomad OTH AF: 0.666

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

GnomAD4 genome AF: 0.648 AC: 98640 AN: 152130 Hom.: 36350 Cov.: 32 AF XY: 0.649 AC XY: 48232 AN XY: 74374

African (AFR) AF: 0.272 AC: 11295 AN: 41490

American (AMR) AF: 0.713 AC: 10897 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.782 AC: 2715 AN: 3472

East Asian (EAS) AF: 0.830 AC: 4301 AN: 5180

South Asian (SAS) AF: 0.639 AC: 3076 AN: 4814

European-Finnish (FIN) AF: 0.806 AC: 8536 AN: 10586

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.816 AC: 55489 AN: 67980

Other (OTH) AF: 0.664 AC: 1403 AN: 2114

Alfa AF: 0.746 Hom.: 15478

Bravo AF: 0.628

Asia WGS AF: 0.699 AC: 2431 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.1
DANN	Benign	0.80
PhyloP100		0.61
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: rs324035; hg19: chr3-113868854;