3-114139503-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000796.6(DRD3):c.720G>A(p.Gln240Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.992 in 1,613,062 control chromosomes in the GnomAD database, including 793,791 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.96 ( 70843 hom., cov: 31)

Exomes 𝑓: 0.99 ( 722948 hom. )

Consequence

DRD3
NM_000796.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 3-114139503-C-T is Benign according to our data. Variant chr3-114139503-C-T is described in ClinVar as [Benign]. Clinvar id is 342598.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.087 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD3	NM_000796.6 link	c.720G>A	p.Gln240Gln	synonymous_variant	Exon 5 of 7	ENST00000383673.5	NP_000787.2	P35462-1X5D2G4A8K8E4
DRD3	NM_001282563.2 link	c.720G>A	p.Gln240Gln	synonymous_variant	Exon 6 of 8		NP_001269492.1	P35462-1X5D2G4A8K8E4
DRD3	NM_001290809.1 link	c.720G>A	p.Gln240Gln	synonymous_variant	Exon 6 of 8		NP_001277738.1	P35462-1X5D2G4A8K8E4A1A4V4
DRD3	NM_033663.6 link	c.720G>A	p.Gln240Gln	synonymous_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>A	p.Gln240Gln	synonymous_variant	Exon 5 of 7	1	NM_000796.6	ENSP00000373169.2		P35462-1

Frequencies

GnomAD3 genomes

AF:

0.963

AC:

146525

AN:

152148

Hom.:

70807

Cov.:

show subpopulations

Gnomad AFR

AF:

0.875

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.987

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.971

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.991

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.974

GnomAD2 exomes

AF:

0.987

AC:

247620

AN:

250788

AF XY:

0.989

show subpopulations

Gnomad AFR exome

AF:

0.874

Gnomad AMR exome

AF:

0.994

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

0.999

Gnomad OTH exome

AF:

0.994

GnomAD4 exome

AF:

0.995

AC:

1452984

AN:

1460796

Hom.:

722948

Cov.:

AF XY:

0.994

AC XY:

722631

AN XY:

726678

show subpopulations

African (AFR)

AF:

0.871

AC:

29144

AN:

33452

American (AMR)

AF:

0.993

AC:

44364

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

26078

AN:

26082

East Asian (EAS)

AF:

1.00

AC:

39691

AN:

39698

South Asian (SAS)

AF:

0.975

AC:

83949

AN:

86110

European-Finnish (FIN)

AF:

1.00

AC:

53399

AN:

53402

Middle Eastern (MID)

AF:

0.990

AC:

5329

AN:

5382

European-Non Finnish (NFE)

AF:

1.00

AC:

1111325

AN:

1111650

Other (OTH)

AF:

0.990

AC:

59705

AN:

60326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

352

704

1055

1407

1759

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.963

AC:

146615

AN:

152266

Hom.:

70843

Cov.:

AF XY:

0.963

AC XY:

71715

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.874

AC:

36289

AN:

41510

American (AMR)

AF:

0.987

AC:

15103

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3472

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5175

AN:

5176

South Asian (SAS)

AF:

0.971

AC:

4680

AN:

4820

European-Finnish (FIN)

AF:

1.00

AC:

10626

AN:

10626

Middle Eastern (MID)

AF:

0.993

AC:

292

AN:

294

European-Non Finnish (NFE)

AF:

0.999

AC:

68009

AN:

68046

Other (OTH)

AF:

0.974

AC:

2057

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

245

490

734

979

1224

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.988

Hom.:

96106

Bravo

AF:

0.959

Asia WGS

AF:

0.982

AC:

3416

AN:

3478

EpiCase

AF:

1.00

EpiControl

AF:

0.999

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Tremor, hereditary essential, 1

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

1.1

(source)

DANN

Benign

0.55

PhyloP100

-0.087

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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3-114139503-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