rs9825563

Positions:

• chr3-114181373-A-G
• chr3-114181373-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001282563.2(DRD3):​c.-155-2597T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 152,064 control chromosomes in the GnomAD database, including 10,295 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 0.36 (10295 hom., cov: 32)
• Consequence: DRD3 NM_001282563.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DRD3	NM_001282563.2	c.-155-2597T>C		intron_variant			NP_001269492.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRD3	ENST00000460779.5	c.-155-2597T>C		intron_variant		2		ENSP00000419402.1

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54287 AN: 151946 Hom.: 10287 Cov.: 32

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.336

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

GnomAD4 genome AF: 0.357 AC: 54346 AN: 152064 Hom.: 10295 Cov.: 32 AF XY: 0.354 AC XY: 26334 AN XY: 74346

Gnomad4 AFR AF: 0.483

Gnomad4 AMR AF: 0.366

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.283

Gnomad4 SAS AF: 0.326

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.337

Alfa AF: 0.320 Hom.: 10678

Bravo AF: 0.372

Asia WGS AF: 0.312 AC: 1086 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs9825563; hg19: chr3-113900220;