3-114128872-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_000796.6(DRD3):c.1047T>C(p.His349=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000659 in 1,611,096 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00062 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00066 (9 hom.)
• Consequence: DRD3 NM_000796.6 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.854

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 3-114128872-A-G is Benign according to our data. Variant chr3-114128872-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 726241.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.854 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DRD3	NM_000796.6	c.1047T>C	p.His349=	synonymous_variant	7/7	ENST00000383673.5
DRD3	NM_001282563.2	c.1047T>C	p.His349=	synonymous_variant	8/8
DRD3	NM_001290809.1	c.1047T>C	p.His349=	synonymous_variant	8/8
DRD3	NM_033663.6	c.948T>C	p.His316=	synonymous_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRD3	ENST00000383673.5	c.1047T>C	p.His349=	synonymous_variant	7/7	1	NM_000796.6	P1

Frequencies

GnomAD3 genomes AF: 0.000618 AC: 94 AN: 152092 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000632

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000917 AC: 228 AN: 248570 Hom.: 0 AF XY: 0.00109 AC XY: 147 AN XY: 134298

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000648

Gnomad ASJ exome AF: 0.00656

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000863

Gnomad FIN exome AF: 0.000278

Gnomad NFE exome AF: 0.000880

Gnomad OTH exome AF: 0.00165

GnomAD4 exome AF: 0.000662 AC: 966 AN: 1458886 Hom.: 9 Cov.: 30 AF XY: 0.000754 AC XY: 547 AN XY: 725588

Gnomad4 AFR exome AF: 0.000330

Gnomad4 AMR exome AF: 0.000679

Gnomad4 ASJ exome AF: 0.00620

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000897

Gnomad4 FIN exome AF: 0.000244

Gnomad4 NFE exome AF: 0.000446

Gnomad4 OTH exome AF: 0.00171

GnomAD4 genome AF: 0.000624 AC: 95 AN: 152210 Hom.: 1 Cov.: 32 AF XY: 0.000551 AC XY: 41 AN XY: 74434

Gnomad4 AFR AF: 0.000193

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.000632

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00105 Hom.: 0

Bravo AF: 0.000669

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00115

EpiControl AF: 0.00119

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jun 09, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2022	DRD3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
Cadd	Benign	2.4
Dann	Benign	0.44

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: rs139341493; hg19: chr3-113847719; COSMIC: COSV55681999;