3-114171942-T-C

Variant names:

• chr3-114171942-T-C
• rs3732783
• NM_000796.6:c.51A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000796.6(DRD3):​c.51A>G​(p.Ala17Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0673 in 1,579,198 control chromosomes in the GnomAD database, including 4,314 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.085 (666 hom., cov: 32)
  • Exomes 𝑓: 0.065 (3648 hom.)
• Consequence: DRD3 NM_000796.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.209
• Publications: 18 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 3-114171942-T-C is Benign according to our data. Variant chr3-114171942-T-C is described in ClinVar as Benign. ClinVar VariationId is 342603.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.209 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.141 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD3	NM_000796.6	MANE Select	c.51A>G	p.Ala17Ala	synonymous	Exon 2 of 7	NP_000787.2	X5D2G4
	DRD3	NM_001282563.2		c.51A>G	p.Ala17Ala	synonymous	Exon 3 of 8	NP_001269492.1	P35462-1
	DRD3	NM_001290809.1		c.51A>G	p.Ala17Ala	synonymous	Exon 3 of 8	NP_001277738.1	X5D2G4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD3	ENST00000383673.5	TSL:1 MANE Select	c.51A>G	p.Ala17Ala	synonymous	Exon 2 of 7	ENSP00000373169.2	P35462-1
	DRD3	ENST00000467632.5	TSL:1	c.51A>G	p.Ala17Ala	synonymous	Exon 3 of 8	ENSP00000420662.1	P35462-1
	DRD3	ENST00000460779.5	TSL:2	c.51A>G	p.Ala17Ala	synonymous	Exon 3 of 8	ENSP00000419402.1	P35462-1

Frequencies

GnomAD3 genomes AF: 0.0852 AC: 12961 AN: 152092 Hom.: 665 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0903

Gnomad ASJ AF: 0.0680

Gnomad EAS AF: 0.0202

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0579

Gnomad OTH AF: 0.0874

GnomAD2 exomes AF: 0.0887 AC: 18136 AN: 204356 AF XY: 0.0880

Gnomad AFR exome AF: 0.121

Gnomad AMR exome AF: 0.142

Gnomad ASJ exome AF: 0.0639

Gnomad EAS exome AF: 0.0182

Gnomad FIN exome AF: 0.118

Gnomad NFE exome AF: 0.0610

Gnomad OTH exome AF: 0.0763

GnomAD4 exome AF: 0.0654 AC: 93307 AN: 1426988 Hom.: 3648 Cov.: 30 AF XY: 0.0671 AC XY: 47435 AN XY: 706628

African (AFR) AF: 0.125 AC: 4064 AN: 32566

American (AMR) AF: 0.131 AC: 5257 AN: 40268

Ashkenazi Jewish (ASJ) AF: 0.0633 AC: 1566 AN: 24726

East Asian (EAS) AF: 0.0180 AC: 686 AN: 38178

South Asian (SAS) AF: 0.141 AC: 11392 AN: 80656

European-Finnish (FIN) AF: 0.106 AC: 5528 AN: 51918

Middle Eastern (MID) AF: 0.0832 AC: 466 AN: 5600

European-Non Finnish (NFE) AF: 0.0551 AC: 60260 AN: 1094158

Other (OTH) AF: 0.0694 AC: 4088 AN: 58918

GnomAD4 genome AF: 0.0853 AC: 12982 AN: 152210 Hom.: 666 Cov.: 32 AF XY: 0.0884 AC XY: 6579 AN XY: 74418

African (AFR) AF: 0.123 AC: 5119 AN: 41534

American (AMR) AF: 0.0907 AC: 1387 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0680 AC: 236 AN: 3470

East Asian (EAS) AF: 0.0203 AC: 105 AN: 5174

South Asian (SAS) AF: 0.150 AC: 722 AN: 4826

European-Finnish (FIN) AF: 0.118 AC: 1254 AN: 10586

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

European-Non Finnish (NFE) AF: 0.0579 AC: 3937 AN: 68006

Other (OTH) AF: 0.0884 AC: 187 AN: 2116

Alfa AF: 0.0680 Hom.: 642

Bravo AF: 0.0832

Asia WGS AF: 0.0850 AC: 297 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	DRD3-related disorder (1)
-	-	1	not provided (1)
-	-	1	Tremor, hereditary essential, 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.83
DANN	Benign	0.34
PhyloP100		-0.21
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: rs3732783; hg19: chr3-113890789;