3-114128901-C-A

Variant names:

• chr3-114128901-C-A
• rs557764679
• NM_000796.6:c.1018G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000796.6(DRD3):​c.1018G>T​(p.Val340Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000113 in 1,598,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000076 (0 hom.)
• Consequence: DRD3 NM_000796.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.985
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19791573).

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.1018G>T	p.Val340Phe	missense	Exon 7 of 7	NP_000787.2	X5D2G4
	DRD3	NM_001282563.2		c.1018G>T	p.Val340Phe	missense	Exon 8 of 8	NP_001269492.1	P35462-1
	DRD3	NM_001290809.1		c.1018G>T	p.Val340Phe	missense	Exon 8 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.1018G>T	p.Val340Phe	missense	Exon 7 of 7	ENSP00000373169.2	P35462-1
	DRD3	ENST00000467632.5	TSL:1	c.1018G>T	p.Val340Phe	missense	Exon 8 of 8	ENSP00000420662.1	P35462-1
	DRD3	ENST00000460779.5	TSL:2	c.1018G>T	p.Val340Phe	missense	Exon 8 of 8	ENSP00000419402.1	P35462-1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152086 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000253 AC: 6 AN: 236722 AF XY: 0.00000783

Gnomad AFR exome AF: 0.000312

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000174

GnomAD4 exome AF: 0.00000760 AC: 11 AN: 1446578 Hom.: 0 Cov.: 30 AF XY: 0.00000417 AC XY: 3 AN XY: 718600

African (AFR) AF: 0.000213 AC: 7 AN: 32934

American (AMR) AF: 0.0000237 AC: 1 AN: 42186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25156

East Asian (EAS) AF: 0.00 AC: 0 AN: 39480

South Asian (SAS) AF: 0.00 AC: 0 AN: 83682

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53042

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1104686

Other (OTH) AF: 0.0000167 AC: 1 AN: 59716

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152204 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74404

African (AFR) AF: 0.000169 AC: 7 AN: 41512

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000986 Hom.: 0

Bravo AF: 0.0000831

ExAC AF: 0.0000412 AC: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.079	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	20
DANN	Benign	0.97
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.061
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.84	T
PhyloP100		0.98
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.37
Sift	Benign	0.33	T
Sift4G	Benign	0.66	T
Polyphen		0.21	B
Vest4		0.37
MVP		0.95
MPC		1.1
ClinPred		0.086	T
GERP RS		2.6
gMVP		0.85
Mutation Taster		=36/64	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs557764679; hg19: chr3-113847748;