rs201369546

Variant names:

• chr3-114139547-G-A
• rs201369546
• NM_000796.6:c.676C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-114139547-G-A
• chr3-114139547-G-C
• chr3-114139547-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000796.6(DRD3):​c.676C>T​(p.Arg226*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: DRD3 NM_000796.6 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.28
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000796.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD3	NM_000796.6	MANE Select	c.676C>T	p.Arg226*	stop_gained	Exon 5 of 7	NP_000787.2	X5D2G4
	DRD3	NM_001282563.2		c.676C>T	p.Arg226*	stop_gained	Exon 6 of 8	NP_001269492.1	P35462-1
	DRD3	NM_001290809.1		c.676C>T	p.Arg226*	stop_gained	Exon 6 of 8	NP_001277738.1	X5D2G4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD3	ENST00000383673.5	TSL:1 MANE Select	c.676C>T	p.Arg226*	stop_gained	Exon 5 of 7	ENSP00000373169.2	P35462-1
	DRD3	ENST00000467632.5	TSL:1	c.676C>T	p.Arg226*	stop_gained	Exon 6 of 8	ENSP00000420662.1	P35462-1
	DRD3	ENST00000460779.5	TSL:2	c.676C>T	p.Arg226*	stop_gained	Exon 6 of 8	ENSP00000419402.1	P35462-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251466 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1461824 Hom.: 0 Cov.: 34 AF XY: 0.0000110 AC XY: 8 AN XY: 727210

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.0000126 AC: 14 AN: 1111980

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000427 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.53	D
BayesDel_noAF	Pathogenic	0.60
CADD	Pathogenic	38
DANN	Uncertain	1.0
Eigen	Pathogenic	0.79
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.93	D
PhyloP100		2.3
Vest4		0.98
GERP RS		5.0
Mutation Taster		=17/183	disease causing (fs/PTC)

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: rs201369546; hg19: chr3-113858394; COSMIC: COSV55678948;