Genetic Variant NM_000796.6:c.723+84C>T (chr3-114139416-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000796.6(DRD3):c.723+84C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0299 in 1,334,702 control chromosomes in the GnomAD database, including 900 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 0.047 ( 259 hom., cov: 33)

Exomes 𝑓: 0.028 ( 641 hom. )

Consequence

DRD3
NM_000796.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.56

Publications

5 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
DRD3	NM_000796.6 link	c.723+84C>T	intron_variant	Intron 5 of 6	ENST00000383673.5	NP_000787.2	P35462-1X5D2G4A8K8E4
DRD3	NM_001282563.2 link	c.723+84C>T	intron_variant	Intron 6 of 7		NP_001269492.1	P35462-1X5D2G4A8K8E4
DRD3	NM_001290809.1 link	c.723+84C>T	intron_variant	Intron 6 of 7		NP_001277738.1	P35462-1X5D2G4A8K8E4A1A4V4
DRD3	NM_033663.6 link	c.723+84C>T	intron_variant	Intron 5 of 7		NP_387512.3	P35462-3E9PCM4A8K8E4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRD3	ENST00000383673.5 link	c.723+84C>T		intron_variant	Intron 5 of 6	1	NM_000796.6	ENSP00000373169.2		P35462-1

Frequencies

GnomAD3 genomes

AF:

0.0468

AC:

7123

AN:

152128

Hom.:

259

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.0235

Gnomad ASJ

AF:

0.0110

Gnomad EAS

AF:

0.00366

Gnomad SAS

AF:

0.0468

Gnomad FIN

AF:

0.0209

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0269

Gnomad OTH

AF:

0.0372

GnomAD4 exome

AF:

0.0277

AC:

32757

AN:

1182456

Hom.:

641

AF XY:

0.0280

AC XY:

16293

AN XY:

582252

show subpopulations

African (AFR)

AF:

0.105

AC:

2854

AN:

27218

American (AMR)

AF:

0.0168

AC:

488

AN:

29000

Ashkenazi Jewish (ASJ)

AF:

0.0104

AC:

192

AN:

18380

East Asian (EAS)

AF:

0.00263

AC:

AN:

36864

South Asian (SAS)

AF:

0.0492

AC:

2701

AN:

54896

European-Finnish (FIN)

AF:

0.0227

AC:

1066

AN:

46978

Middle Eastern (MID)

AF:

0.0419

AC:

139

AN:

3320

European-Non Finnish (NFE)

AF:

0.0259

AC:

23752

AN:

916478

Other (OTH)

AF:

0.0298

AC:

1468

AN:

49322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1511

3022

4532

6043

7554

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

976

1952

2928

3904

4880

<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:

0.0469

AC:

7146

AN:

152246

Hom.:

259

Cov.:

AF XY:

0.0465

AC XY:

3464

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.105

AC:

4340

AN:

41528

American (AMR)

AF:

0.0234

AC:

358

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0110

AC:

AN:

3470

East Asian (EAS)

AF:

0.00366

AC:

AN:

5186

South Asian (SAS)

AF:

0.0466

AC:

225

AN:

4826

European-Finnish (FIN)

AF:

0.0209

AC:

222

AN:

10598

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0270

AC:

1834

AN:

68016

Other (OTH)

AF:

0.0369

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

340

680

1020

1360

1700

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

258

344

430

<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:

0.0324

Hom.:

139

Bravo

AF:

0.0487

Asia WGS

AF:

0.0280

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

9.8

(source)

DANN

Benign

0.47

PhyloP100

1.6

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over