3-114162594-G-C

Variant names:

• chr3-114162594-G-C
• rs324030
• NM_000796.6:c.271-2727C>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.271-2727C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 152,138 control chromosomes in the GnomAD database, including 29,248 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 0.60 (29248 hom., cov: 33)
• Consequence: DRD3 NM_000796.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.376
• Publications: 4 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000796.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD3	NM_000796.6	MANE Select	c.271-2727C>G		intron	N/A	NP_000787.2
	DRD3	NM_001282563.2		c.271-2727C>G		intron	N/A	NP_001269492.1
	DRD3	NM_001290809.1		c.271-2727C>G		intron	N/A	NP_001277738.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD3	ENST00000383673.5	TSL:1 MANE Select	c.271-2727C>G		intron	N/A	ENSP00000373169.2
	DRD3	ENST00000467632.5	TSL:1	c.271-2727C>G		intron	N/A	ENSP00000420662.1
	DRD3	ENST00000460779.5	TSL:2	c.271-2727C>G		intron	N/A	ENSP00000419402.1

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90827 AN: 152020 Hom.: 29245 Cov.: 33

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.739

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.716

Gnomad EAS AF: 0.721

Gnomad SAS AF: 0.662

Gnomad FIN AF: 0.696

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.617

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

GnomAD4 genome AF: 0.597 AC: 90866 AN: 152138 Hom.: 29248 Cov.: 33 AF XY: 0.596 AC XY: 44341 AN XY: 74382

African (AFR) AF: 0.345 AC: 14320 AN: 41482

American (AMR) AF: 0.567 AC: 8671 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.716 AC: 2485 AN: 3472

East Asian (EAS) AF: 0.721 AC: 3731 AN: 5176

South Asian (SAS) AF: 0.662 AC: 3195 AN: 4824

European-Finnish (FIN) AF: 0.696 AC: 7357 AN: 10578

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.720 AC: 48944 AN: 67992

Other (OTH) AF: 0.618 AC: 1305 AN: 2112

Alfa AF: 0.579 Hom.: 2027

Bravo AF: 0.578

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.0
DANN	Benign	0.55
PhyloP100		0.38
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: rs324030; hg19: chr3-113881441;