3-114171942-T-C

Variant names:

• chr3-114171942-T-C
• rs3732783
• NM_000796.6:c.51A>G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000796.6(DRD3):​c.51A>G​(p.Ala17Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0673 in 1,579,198 control chromosomes in the GnomAD database, including 4,314 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.085 (666 hom., cov: 32)
  • Exomes 𝑓: 0.065 (3648 hom.)
• Consequence: DRD3 NM_000796.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.209

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 3-114171942-T-C is Benign according to our data. Variant chr3-114171942-T-C is described in ClinVar as [Benign]. Clinvar id is 342603.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.209 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD3	NM_000796.6	c.51A>G	p.Ala17Ala	synonymous_variant	Exon 2 of 7	ENST00000383673.5	NP_000787.2
DRD3	NM_001282563.2	c.51A>G	p.Ala17Ala	synonymous_variant	Exon 3 of 8		NP_001269492.1
DRD3	NM_001290809.1	c.51A>G	p.Ala17Ala	synonymous_variant	Exon 3 of 8		NP_001277738.1
DRD3	NM_033663.6	c.51A>G	p.Ala17Ala	synonymous_variant	Exon 2 of 8		NP_387512.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRD3	ENST00000383673.5	c.51A>G	p.Ala17Ala	synonymous_variant	Exon 2 of 7	1	NM_000796.6	ENSP00000373169.2

Frequencies

GnomAD3 genomes AF: 0.0852 AC: 12961 AN: 152092 Hom.: 665 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0903

Gnomad ASJ AF: 0.0680

Gnomad EAS AF: 0.0202

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0579

Gnomad OTH AF: 0.0874

GnomAD3 exomes AF: 0.0887 AC: 18136 AN: 204356 Hom.: 986 AF XY: 0.0880 AC XY: 9698 AN XY: 110186

Gnomad AFR exome AF: 0.121

Gnomad AMR exome AF: 0.142

Gnomad ASJ exome AF: 0.0639

Gnomad EAS exome AF: 0.0182

Gnomad SAS exome AF: 0.146

Gnomad FIN exome AF: 0.118

Gnomad NFE exome AF: 0.0610

Gnomad OTH exome AF: 0.0763

GnomAD4 exome AF: 0.0654 AC: 93307 AN: 1426988 Hom.: 3648 Cov.: 30 AF XY: 0.0671 AC XY: 47435 AN XY: 706628

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.131

Gnomad4 ASJ exome AF: 0.0633

Gnomad4 EAS exome AF: 0.0180

Gnomad4 SAS exome AF: 0.141

Gnomad4 FIN exome AF: 0.106

Gnomad4 NFE exome AF: 0.0551

Gnomad4 OTH exome AF: 0.0694

GnomAD4 genome AF: 0.0853 AC: 12982 AN: 152210 Hom.: 666 Cov.: 32 AF XY: 0.0884 AC XY: 6579 AN XY: 74418

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.0907

Gnomad4 ASJ AF: 0.0680

Gnomad4 EAS AF: 0.0203

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.0579

Gnomad4 OTH AF: 0.0884

Alfa AF: 0.0660 Hom.: 493

Bravo AF: 0.0832

Asia WGS AF: 0.0850 AC: 297 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

DRD3-related disorder Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

Jan 12, 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	-0.85
CADD	Benign	0.83
DANN	Benign	0.34

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

Other links and lift over

dbSNP: rs3732783; hg19: chr3-113890789;