3-114131363-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000796.6(DRD3):c.761G>A(p.Arg254His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

DRD3
NM_000796.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.33

Publications

3 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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22444561).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD3	NM_000796.6 link	c.761G>A	p.Arg254His	missense_variant	Exon 6 of 7	ENST00000383673.5	NP_000787.2	P35462-1X5D2G4A8K8E4
DRD3	NM_001282563.2 link	c.761G>A	p.Arg254His	missense_variant	Exon 7 of 8		NP_001269492.1	P35462-1X5D2G4A8K8E4
DRD3	NM_001290809.1 link	c.761G>A	p.Arg254His	missense_variant	Exon 7 of 8		NP_001277738.1	P35462-1X5D2G4A8K8E4A1A4V4
DRD3	NM_033663.6 link	c.761G>A	p.Arg254His	missense_variant	Exon 6 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.761G>A	p.Arg254His	missense_variant	Exon 6 of 7	1	NM_000796.6	ENSP00000373169.2		P35462-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000159

AC:

AN:

251370

AF XY:

0.0000221

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461862

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1111988

Other (OTH)

AF:

0.0000166

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 21, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.761G>A (p.R254H) alteration is located in exon 6 (coding exon 5) of the DRD3 gene. This alteration results from a G to A substitution at nucleotide position 761, causing the arginine (R) at amino acid position 254 to be replaced by a histidine (H). 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

Benign

0.074

BayesDel_addAF

Benign

-0.085

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.034

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.76

.;.;T;T

M_CAP

Benign

0.063

MetaRNN

Benign

0.22

T;T;T;T

MetaSVM

Benign

-0.59

PhyloP100

1.3

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.91

N;N;N;N

REVEL

Benign

0.23

Sift

Benign

0.033

D;D;T;D

Sift4G

Benign

0.091

T;T;T;T

Polyphen

0.89

.;.;P;.

Vest4

0.22

MVP

0.93

MPC

0.46

ClinPred

0.15

GERP RS

4.8

gMVP

0.32

Mutation Taster

=79/21

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

3-114131363-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over