3-114128872-A-G

Variant names:

• chr3-114128872-A-G
• rs139341493
• NM_000796.6:c.1047T>C

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_000796.6(DRD3):​c.1047T>C​(p.His349His) 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:3
• Conservation: PhyloP100: 0.854
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.052).
• 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.
• BS2: High Homozygotes in GnomAdExome4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD3	NM_000796.6	c.1047T>C	p.His349His	synonymous_variant	Exon 7 of 7	ENST00000383673.5	NP_000787.2
DRD3	NM_001282563.2	c.1047T>C	p.His349His	synonymous_variant	Exon 8 of 8		NP_001269492.1
DRD3	NM_001290809.1	c.1047T>C	p.His349His	synonymous_variant	Exon 8 of 8		NP_001277738.1
DRD3	NM_033663.6	c.948T>C	p.His316His	synonymous_variant	Exon 8 of 8		NP_387512.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRD3	ENST00000383673.5	c.1047T>C	p.His349His	synonymous_variant	Exon 7 of 7	1	NM_000796.6	ENSP00000373169.2

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

GnomAD2 exomes AF: 0.000917 AC: 228 AN: 248570 AF XY: 0.00109

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 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

African (AFR) AF: 0.000330 AC: 11 AN: 33358

American (AMR) AF: 0.000679 AC: 30 AN: 44180

Ashkenazi Jewish (ASJ) AF: 0.00620 AC: 161 AN: 25966

East Asian (EAS) AF: 0.00 AC: 0 AN: 39642

South Asian (SAS) AF: 0.000897 AC: 77 AN: 85794

European-Finnish (FIN) AF: 0.000244 AC: 13 AN: 53358

Middle Eastern (MID) AF: 0.0132 AC: 76 AN: 5762

European-Non Finnish (NFE) AF: 0.000446 AC: 495 AN: 1110566

Other (OTH) AF: 0.00171 AC: 103 AN: 60260

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

African (AFR) AF: 0.000193 AC: 8 AN: 41536

American (AMR) AF: 0.00111 AC: 17 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 17 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4824

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10608

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000632 AC: 43 AN: 68004

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Nov 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

DRD3: BP4, BP7 -

Jun 09, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely 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	-0.56
CADD	Benign	2.4
DANN	Benign	0.44
PhyloP100		0.85
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

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