chr3-114139503-C-T

Variant names:

• chr3-114139503-C-T
• rs2251177
• NM_000796.6:c.720G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_000796.6(DRD3):​c.720G>A​(p.Gln240Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.992 in 1,613,062 control chromosomes in the GnomAD database, including 793,791 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.96 (70843 hom., cov: 31)
  • Exomes 𝑓: 0.99 (722948 hom.)
• Consequence: DRD3 NM_000796.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0870
• 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 3-114139503-C-T is Benign according to our data. Variant chr3-114139503-C-T is described in ClinVar as Benign. ClinVar VariationId is 342598.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.087 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 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.720G>A	p.Gln240Gln	synonymous	Exon 5 of 7	NP_000787.2	X5D2G4
	DRD3	NM_001282563.2		c.720G>A	p.Gln240Gln	synonymous	Exon 6 of 8	NP_001269492.1	P35462-1
	DRD3	NM_001290809.1		c.720G>A	p.Gln240Gln	synonymous	Exon 6 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.720G>A	p.Gln240Gln	synonymous	Exon 5 of 7	ENSP00000373169.2	P35462-1
	DRD3	ENST00000467632.5	TSL:1	c.720G>A	p.Gln240Gln	synonymous	Exon 6 of 8	ENSP00000420662.1	P35462-1
	DRD3	ENST00000460779.5	TSL:2	c.720G>A	p.Gln240Gln	synonymous	Exon 6 of 8	ENSP00000419402.1	P35462-1

Frequencies

GnomAD3 genomes AF: 0.963 AC: 146525 AN: 152148 Hom.: 70807 Cov.: 31

Gnomad AFR AF: 0.875

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.987

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.971

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.974

GnomAD2 exomes AF: 0.987 AC: 247620 AN: 250788 AF XY: 0.989

Gnomad AFR exome AF: 0.874

Gnomad AMR exome AF: 0.994

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 0.999

Gnomad OTH exome AF: 0.994

GnomAD4 exome AF: 0.995 AC: 1452984 AN: 1460796 Hom.: 722948 Cov.: 45 AF XY: 0.994 AC XY: 722631 AN XY: 726678

African (AFR) AF: 0.871 AC: 29144 AN: 33452

American (AMR) AF: 0.993 AC: 44364 AN: 44694

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 26078 AN: 26082

East Asian (EAS) AF: 1.00 AC: 39691 AN: 39698

South Asian (SAS) AF: 0.975 AC: 83949 AN: 86110

European-Finnish (FIN) AF: 1.00 AC: 53399 AN: 53402

Middle Eastern (MID) AF: 0.990 AC: 5329 AN: 5382

European-Non Finnish (NFE) AF: 1.00 AC: 1111325 AN: 1111650

Other (OTH) AF: 0.990 AC: 59705 AN: 60326

GnomAD4 genome AF: 0.963 AC: 146615 AN: 152266 Hom.: 70843 Cov.: 31 AF XY: 0.963 AC XY: 71715 AN XY: 74436

African (AFR) AF: 0.874 AC: 36289 AN: 41510

American (AMR) AF: 0.987 AC: 15103 AN: 15298

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5175 AN: 5176

South Asian (SAS) AF: 0.971 AC: 4680 AN: 4820

European-Finnish (FIN) AF: 1.00 AC: 10626 AN: 10626

Middle Eastern (MID) AF: 0.993 AC: 292 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 68009 AN: 68046

Other (OTH) AF: 0.974 AC: 2057 AN: 2112

Alfa AF: 0.988 Hom.: 96106

Bravo AF: 0.959

Asia WGS AF: 0.982 AC: 3416 AN: 3478

EpiCase AF: 1.00

EpiControl AF: 0.999

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	1.1
DANN	Benign	0.55
PhyloP100		-0.087
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: rs2251177; hg19: chr3-113858350; COSMIC: COSV108094336;