Genetic Variant DRD3:p.Gln240His (chr3-114139503-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_000796.6(DRD3):c.720G>C(p.Gln240His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q240Q) has been classified as Benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DRD3
NM_000796.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0870

Publications

18 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:

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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=0.10918027).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD3	NM_000796.6 link	c.720G>C	p.Gln240His	missense_variant	Exon 5 of 7	ENST00000383673.5	NP_000787.2	P35462-1X5D2G4A8K8E4
DRD3	NM_001282563.2 link	c.720G>C	p.Gln240His	missense_variant	Exon 6 of 8		NP_001269492.1	P35462-1X5D2G4A8K8E4
DRD3	NM_001290809.1 link	c.720G>C	p.Gln240His	missense_variant	Exon 6 of 8		NP_001277738.1	P35462-1X5D2G4A8K8E4A1A4V4
DRD3	NM_033663.6 link	c.720G>C	p.Gln240His	missense_variant	Exon 5 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.720G>C	p.Gln240His	missense_variant	Exon 5 of 7	1	NM_000796.6	ENSP00000373169.2		P35462-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1460804

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726680

African (AFR)

AF:

0.00

AC:

AN:

33456

American (AMR)

AF:

0.00

AC:

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26082

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86110

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5384

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111652

Other (OTH)

AF:

0.00

AC:

AN:

60326

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.080

BayesDel_noAF

Benign

-0.35

CADD

Benign

7.7

(source)

DANN

Uncertain

0.98

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.65

.;.;T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.11

T;T;T;T

MetaSVM

Benign

-0.99

PhyloP100

-0.087

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.80

N;N;N;N

REVEL

Benign

0.20

Sift

Benign

0.099

T;T;T;T

Sift4G

Benign

0.13

T;T;T;T

Polyphen

0.0010

.;.;B;.

Vest4

0.11

MutPred

0.48

Loss of disorder (P = 0.1258);Loss of disorder (P = 0.1258);Loss of disorder (P = 0.1258);Loss of disorder (P = 0.1258);

MVP

0.86

MPC

0.35

ClinPred

0.085

GERP RS

0.029

gMVP

0.38

Mutation Taster

=93/7

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over