rs16822416

Variant names:

• chr3-114171463-G-A
• rs16822416
• NM_000796.6:c.270+260C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-114171463-G-A
• chr3-114171463-G-T

Variant summary

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

The NM_000796.6(DRD3):​c.270+260C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0845 in 152,026 control chromosomes in the GnomAD database, including 644 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 0.084 (644 hom., cov: 32)
• Consequence: DRD3 NM_000796.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.418
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.126 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.270+260C>T		intron	N/A	NP_000787.2
	DRD3	NM_001282563.2		c.270+260C>T		intron	N/A	NP_001269492.1
	DRD3	NM_001290809.1		c.270+260C>T		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.270+260C>T		intron	N/A	ENSP00000373169.2
	DRD3	ENST00000467632.5	TSL:1	c.270+260C>T		intron	N/A	ENSP00000420662.1
	DRD3	ENST00000460779.5	TSL:2	c.270+260C>T		intron	N/A	ENSP00000419402.1

Frequencies

GnomAD3 genomes AF: 0.0844 AC: 12821 AN: 151910 Hom.: 642 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.0165

Gnomad AMR AF: 0.0914

Gnomad ASJ AF: 0.0681

Gnomad EAS AF: 0.0104

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0578

Gnomad OTH AF: 0.0869

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

GnomAD4 genome AF: 0.0845 AC: 12839 AN: 152026 Hom.: 644 Cov.: 32 AF XY: 0.0874 AC XY: 6495 AN XY: 74286

African (AFR) AF: 0.123 AC: 5102 AN: 41452

American (AMR) AF: 0.0918 AC: 1402 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0681 AC: 236 AN: 3466

East Asian (EAS) AF: 0.0104 AC: 54 AN: 5176

South Asian (SAS) AF: 0.135 AC: 646 AN: 4802

European-Finnish (FIN) AF: 0.119 AC: 1253 AN: 10564

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0578 AC: 3928 AN: 67984

Other (OTH) AF: 0.0870 AC: 183 AN: 2104

Alfa AF: 0.0652 Hom.: 548

Bravo AF: 0.0827

Asia WGS AF: 0.0770 AC: 269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.52
PhyloP100		-0.42
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: rs16822416; hg19: chr3-113890310;