3-114128747-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PP3_Strong

The NM_000796.6(DRD3):c.1172G>A(p.Arg391Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,608,130 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

DRD3
NM_000796.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91

Publications

2 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: Uncertain_significance. The variant received 4 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.957

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD3	NM_000796.6 link	c.1172G>A	p.Arg391Gln	missense_variant	Exon 7 of 7	ENST00000383673.5	NP_000787.2	P35462-1X5D2G4A8K8E4
DRD3	NM_001282563.2 link	c.1172G>A	p.Arg391Gln	missense_variant	Exon 8 of 8		NP_001269492.1	P35462-1X5D2G4A8K8E4
DRD3	NM_001290809.1 link	c.1172G>A	p.Arg391Gln	missense_variant	Exon 8 of 8		NP_001277738.1	P35462-1X5D2G4A8K8E4A1A4V4
DRD3	NM_033663.6 link	c.1073G>A	p.Arg358Gln	missense_variant	Exon 8 of 8		NP_387512.3	P35462-3E9PCM4A8K8E4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRD3	ENST00000383673.5 link	c.1172G>A	p.Arg391Gln	missense_variant	Exon 7 of 7	1	NM_000796.6	ENSP00000373169.2		P35462-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152012

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000891

AC:

AN:

246850

AF XY:

0.0000975

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000504

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000895

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000206

AC:

AN:

1456118

Hom.:

Cov.:

AF XY:

0.0000262

AC XY:

AN XY:

724024

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33288

American (AMR)

AF:

0.000388

AC:

AN:

43848

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25812

East Asian (EAS)

AF:

0.0000505

AC:

AN:

39614

South Asian (SAS)

AF:

0.0000820

AC:

AN:

85334

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53292

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5732

European-Non Finnish (NFE)

AF:

0.00000271

AC:

AN:

1109052

Other (OTH)

AF:

0.00

AC:

AN:

60146

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152012

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74244

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41382

American (AMR)

AF:

0.0000656

AC:

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000741

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 08, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1172G>A (p.R391Q) alteration is located in exon 7 (coding exon 6) of the DRD3 gene. This alteration results from a G to A substitution at nucleotide position 1172, causing the arginine (R) at amino acid position 391 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Uncertain

0.080

BayesDel_noAF

Pathogenic

0.22

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Uncertain

0.93

LIST_S2

Pathogenic

0.99

.;.;D;D

M_CAP

Benign

0.041

MetaRNN

Pathogenic

0.96

D;D;D;D

MetaSVM

Benign

-0.65

PhyloP100

7.9

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-3.2

D;D;D;D

REVEL

Uncertain

0.53

Sift

Pathogenic

0.0

D;D;T;D

Sift4G

Uncertain

0.0030

D;D;D;D

Polyphen

1.0

.;.;D;.

Vest4

0.96

MutPred

0.88

Loss of MoRF binding (P = 0.0274);Loss of MoRF binding (P = 0.0274);.;Loss of MoRF binding (P = 0.0274);

MVP

0.91

MPC

1.3

ClinPred

0.92

GERP RS

5.4

gMVP

0.94

Mutation Taster

=23/77

disease causing

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

3-114128747-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over