NM_001282563.2:c.-155-8603T>G

Variant names:

• chr3-114187379-A-C
• rs1354348
• NM_001282563.2:c.-155-8603T>G

Variant summary

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

The NM_001282563.2(DRD3):​c.-155-8603T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0737 in 152,240 control chromosomes in the GnomAD database, including 585 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 (585 hom., cov: 32)
• Consequence: DRD3 NM_001282563.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.18
• Publications: 2 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD3	NM_001282563.2	c.-155-8603T>G		intron_variant	Intron 1 of 7		NP_001269492.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRD3	ENST00000460779.5	c.-155-8603T>G		intron_variant	Intron 1 of 7	2		ENSP00000419402.1

Frequencies

GnomAD3 genomes AF: 0.0737 AC: 11215 AN: 152122 Hom.: 586 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.0560

Gnomad AMR AF: 0.0563

Gnomad ASJ AF: 0.0481

Gnomad EAS AF: 0.0465

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.0571

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0419

Gnomad OTH AF: 0.0813

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

GnomAD4 genome AF: 0.0737 AC: 11223 AN: 152240 Hom.: 585 Cov.: 32 AF XY: 0.0735 AC XY: 5474 AN XY: 74440

African (AFR) AF: 0.138 AC: 5722 AN: 41526

American (AMR) AF: 0.0563 AC: 861 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0481 AC: 167 AN: 3472

East Asian (EAS) AF: 0.0464 AC: 240 AN: 5170

South Asian (SAS) AF: 0.108 AC: 521 AN: 4826

European-Finnish (FIN) AF: 0.0571 AC: 606 AN: 10610

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0419 AC: 2851 AN: 68018

Other (OTH) AF: 0.0823 AC: 174 AN: 2114

Alfa AF: 0.0444 Hom.: 85

Bravo AF: 0.0740

Asia WGS AF: 0.0930 AC: 323 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	11
DANN	Benign	0.58
PhyloP100		2.2
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: rs1354348; hg19: chr3-113906226;