rs9288993

Variant names:

• chr3-114140326-A-G
• rs9288993
• NM_000796.6:c.527-630T>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.527-630T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0742 in 152,236 control chromosomes in the GnomAD database, including 892 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 0.074 (892 hom., cov: 32)
• Consequence: DRD3 NM_000796.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.796
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD3	NM_000796.6	c.527-630T>C		intron_variant	Intron 4 of 6	ENST00000383673.5	NP_000787.2
DRD3	NM_001282563.2	c.527-630T>C		intron_variant	Intron 5 of 7		NP_001269492.1
DRD3	NM_001290809.1	c.527-630T>C		intron_variant	Intron 5 of 7		NP_001277738.1
DRD3	NM_033663.6	c.527-630T>C		intron_variant	Intron 4 of 7		NP_387512.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRD3	ENST00000383673.5	c.527-630T>C		intron_variant	Intron 4 of 6	1	NM_000796.6	ENSP00000373169.2

Frequencies

GnomAD3 genomes AF: 0.0740 AC: 11258 AN: 152118 Hom.: 888 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0325

Gnomad ASJ AF: 0.0110

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0487

Gnomad FIN AF: 0.0209

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0273

Gnomad OTH AF: 0.0560

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

GnomAD4 genome AF: 0.0742 AC: 11293 AN: 152236 Hom.: 892 Cov.: 32 AF XY: 0.0731 AC XY: 5441 AN XY: 74448

African (AFR) AF: 0.200 AC: 8293 AN: 41510

American (AMR) AF: 0.0324 AC: 496 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0110 AC: 38 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.0483 AC: 233 AN: 4826

European-Finnish (FIN) AF: 0.0209 AC: 222 AN: 10622

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0273 AC: 1855 AN: 68014

Other (OTH) AF: 0.0554 AC: 117 AN: 2112

Alfa AF: 0.0394 Hom.: 1230

Bravo AF: 0.0800

Asia WGS AF: 0.0380 AC: 132 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.31
DANN	Benign	0.72
PhyloP100		-0.80
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: rs9288993; hg19: chr3-113859173;