rs6280

Positions:

chr3-114171968-C-T

Variant summary

Our verdict is Benign. Variant got -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. 14/18 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

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 made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DRD3	NM_000796.6 linkuse as main transcript	c.25G>A	p.Gly9Ser	missense_variant	2/7	ENST00000383673.5	NP_000787.2
DRD3	NM_001282563.2 linkuse as main transcript	c.25G>A	p.Gly9Ser	missense_variant	3/8		NP_001269492.1
DRD3	NM_001290809.1 linkuse as main transcript	c.25G>A	p.Gly9Ser	missense_variant	3/8		NP_001277738.1
DRD3	NM_033663.6 linkuse as main transcript	c.25G>A	p.Gly9Ser	missense_variant	2/8		NP_387512.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRD3	ENST00000383673.5 linkuse as main transcript	c.25G>A	p.Gly9Ser	missense_variant	2/7	1	NM_000796.6	ENSP00000373169	P1	P35462-1

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

GnomAD3 exomes

AF:

0.628

AC:

95572

AN:

152300

Hom.:

30801

AF XY:

0.634

AC XY:

51824

AN XY:

81692

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 SAS exome

AF:

0.592

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

Gnomad4 AFR exome

AF:

0.245

Gnomad4 AMR exome

AF:

0.547

Gnomad4 ASJ exome

AF:

0.714

Gnomad4 EAS exome

AF:

0.714

Gnomad4 SAS exome

AF:

0.586

Gnomad4 FIN exome

AF:

0.675

Gnomad4 NFE exome

AF:

0.669

Gnomad4 OTH exome

AF:

0.630

GnomAD4 genome

AF:

0.547

AC:

83186

AN:

152088

Hom.:

25265

Cov.:

AF XY:

0.547

AC XY:

40624

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.269

Gnomad4 AMR

AF:

0.547

Gnomad4 ASJ

AF:

0.707

Gnomad4 EAS

AF:

0.698

Gnomad4 SAS

AF:

0.591

Gnomad4 FIN

AF:

0.662

Gnomad4 NFE

AF:

0.673

Gnomad4 OTH

AF:

0.587

Alfa

AF:

0.651

Hom.:

80419

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

Significance: Benign/Likely benign

Submissions summary: Benign:4Other:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 09, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

DRD3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 27, 2024

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Tremor, hereditary essential, 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Mar 06, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Schizophrenia, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Mar 06, 2007

- -

Essential tremor, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Mar 06, 2007

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.082

DANN

Benign

0.82

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0036

LIST_S2

Benign

0.41

.;.;T;T

MetaRNN

Benign

0.0000022

T;T;T;T

MetaSVM

Benign

-0.93

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.34

PROVEAN

Benign

0.98

N;N;N;N

REVEL

Benign

0.033

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0

.;.;B;.

Vest4

0.022

MPC

0.37

ClinPred

0.00050

GERP RS

-1.5

gMVP

0.29

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over