rs6280

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000796.6(DRD3):c.25G>A(p.Gly9Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 1,496,244 control chromosomes in the GnomAD database, including 316,020 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 25265 hom., cov: 32)

Exomes 𝑓: 0.65 ( 290755 hom. )

Consequence

DRD3
NM_000796.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4O:2

Conservation

PhyloP100: -0.471

Publications

550 publications found

Variant links:

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]

DRD3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.230764E-6).

BP6

Variant 3-114171968-C-T is Benign according to our data. Variant chr3-114171968-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 16770.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.679 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DRD3	NM_000796.6	MANE Select	c.25G>A	p.Gly9Ser	missense	Exon 2 of 7	NP_000787.2
DRD3	NM_001282563.2		c.25G>A	p.Gly9Ser	missense	Exon 3 of 8	NP_001269492.1
DRD3	NM_001290809.1		c.25G>A	p.Gly9Ser	missense	Exon 3 of 8	NP_001277738.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DRD3	ENST00000383673.5	TSL:1 MANE Select	c.25G>A	p.Gly9Ser	missense	Exon 2 of 7	ENSP00000373169.2
DRD3	ENST00000467632.5	TSL:1	c.25G>A	p.Gly9Ser	missense	Exon 3 of 8	ENSP00000420662.1
DRD3	ENST00000460779.5	TSL:2	c.25G>A	p.Gly9Ser	missense	Exon 3 of 8	ENSP00000419402.1

Frequencies

GnomAD3 genomes

AF:

0.547

AC:

83156

AN:

151970

Hom.:

25266

Cov.:

show subpopulations

Gnomad AFR

AF:

0.269

Gnomad AMI

AF:

0.648

Gnomad AMR

AF:

0.547

Gnomad ASJ

AF:

0.707

Gnomad EAS

AF:

0.698

Gnomad SAS

AF:

0.590

Gnomad FIN

AF:

0.662

Gnomad MID

AF:

0.601

Gnomad NFE

AF:

0.673

Gnomad OTH

AF:

0.588

GnomAD2 exomes

AF:

0.628

AC:

95572

AN:

152300

AF XY:

0.634

show subpopulations

Gnomad AFR exome

AF:

0.263

Gnomad AMR exome

AF:

0.549

Gnomad ASJ exome

AF:

0.726

Gnomad EAS exome

AF:

0.696

Gnomad FIN exome

AF:

0.674

Gnomad NFE exome

AF:

0.680

Gnomad OTH exome

AF:

0.662

GnomAD4 exome

AF:

0.653

AC:

877824

AN:

1344156

Hom.:

290755

Cov.:

AF XY:

0.653

AC XY:

429752

AN XY:

658204

show subpopulations

African (AFR)

AF:

0.245

AC:

7333

AN:

29874

American (AMR)

AF:

0.547

AC:

16484

AN:

30138

Ashkenazi Jewish (ASJ)

AF:

0.714

AC:

15524

AN:

21728

East Asian (EAS)

AF:

0.714

AC:

24435

AN:

34204

South Asian (SAS)

AF:

0.586

AC:

40571

AN:

69272

European-Finnish (FIN)

AF:

0.675

AC:

33527

AN:

49682

Middle Eastern (MID)

AF:

0.636

AC:

3352

AN:

5270

European-Non Finnish (NFE)

AF:

0.669

AC:

701716

AN:

1048600

Other (OTH)

AF:

0.630

AC:

34882

AN:

55388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

16279

32558

48838

65117

81396

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18712

37424

56136

74848

93560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.547

AC:

83186

AN:

152088

Hom.:

25265

Cov.:

AF XY:

0.547

AC XY:

40624

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.269

AC:

11172

AN:

41492

American (AMR)

AF:

0.547

AC:

8354

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.707

AC:

2455

AN:

3470

East Asian (EAS)

AF:

0.698

AC:

3607

AN:

5166

South Asian (SAS)

AF:

0.591

AC:

2847

AN:

4820

European-Finnish (FIN)

AF:

0.662

AC:

6995

AN:

10572

Middle Eastern (MID)

AF:

0.609

AC:

179

AN:

294

European-Non Finnish (NFE)

AF:

0.673

AC:

45747

AN:

67968

Other (OTH)

AF:

0.587

AC:

1239

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1702

3405

5107

6810

8512

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

708

1416

2124

2832

3540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.637

Hom.:

152881

Bravo

AF:

0.528

TwinsUK

AF:

0.662

AC:

2454

ALSPAC

AF:

0.662

AC:

2551

ESP6500AA

AF:

0.276

AC:

1216

ESP6500EA

AF:

0.666

AC:

5723

ExAC

AF:

0.585

AC:

70275

Asia WGS

AF:

0.615

AC:

2140

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

DRD3-related disorder (1)

not provided (1)

not specified (1)

Tremor, hereditary essential, 1 (1)

Essential tremor, susceptibility to (1)

Schizophrenia, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.082

(source)

DANN

Benign

0.82

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0036

LIST_S2

Benign

0.41

MetaRNN

Benign

0.0000022

MetaSVM

Benign

-0.93

PhyloP100

-0.47

PrimateAI

Benign

0.34

PROVEAN

Benign

0.98

REVEL

Benign

0.033

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.022

MPC

0.37

ClinPred

0.00050

GERP RS

-1.5

gMVP

0.29

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over