NM_000796.6:c.383+3543T>C

Variant names:

• chr3-114156212-A-G
• rs2630351
• NM_000796.6:c.383+3543T>C

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+3543T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.923 in 152,290 control chromosomes in the GnomAD database, including 64,940 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 0.92 (64940 hom., cov: 32)
• Consequence: DRD3 NM_000796.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00900
• Publications: 13 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD3	NM_000796.6	c.383+3543T>C		intron_variant	Intron 3 of 6	ENST00000383673.5	NP_000787.2
DRD3	NM_001282563.2	c.383+3543T>C		intron_variant	Intron 4 of 7		NP_001269492.1
DRD3	NM_001290809.1	c.383+3543T>C		intron_variant	Intron 4 of 7		NP_001277738.1
DRD3	NM_033663.6	c.383+3543T>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.383+3543T>C		intron_variant	Intron 3 of 6	1	NM_000796.6	ENSP00000373169.2

Frequencies

GnomAD3 genomes AF: 0.923 AC: 140460 AN: 152172 Hom.: 64915 Cov.: 32

Gnomad AFR AF: 0.887

Gnomad AMI AF: 0.862

Gnomad AMR AF: 0.919

Gnomad ASJ AF: 0.971

Gnomad EAS AF: 0.896

Gnomad SAS AF: 0.930

Gnomad FIN AF: 0.955

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.941

Gnomad OTH AF: 0.925

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

GnomAD4 genome AF: 0.923 AC: 140538 AN: 152290 Hom.: 64940 Cov.: 32 AF XY: 0.923 AC XY: 68768 AN XY: 74472

African (AFR) AF: 0.886 AC: 36814 AN: 41538

American (AMR) AF: 0.918 AC: 14053 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.971 AC: 3369 AN: 3470

East Asian (EAS) AF: 0.896 AC: 4638 AN: 5176

South Asian (SAS) AF: 0.931 AC: 4493 AN: 4828

European-Finnish (FIN) AF: 0.955 AC: 10151 AN: 10628

Middle Eastern (MID) AF: 0.918 AC: 270 AN: 294

European-Non Finnish (NFE) AF: 0.941 AC: 64016 AN: 68030

Other (OTH) AF: 0.922 AC: 1950 AN: 2114

Alfa AF: 0.938 Hom.: 41083

Bravo AF: 0.918

Asia WGS AF: 0.918 AC: 3193 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.8
DANN	Benign	0.73
PhyloP100		0.0090
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: rs2630351; hg19: chr3-113875059;