rs769658489

Variant names:

• chr3-114128789-G-A
• rs769658489
• NM_000796.6:c.1130C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-114128789-G-A
• chr3-114128789-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_000796.6(DRD3):​c.1130C>T​(p.Ala377Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A377D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DRD3 NM_000796.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 10.0
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.911

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD3	NM_000796.6	c.1130C>T	p.Ala377Val	missense_variant	Exon 7 of 7	ENST00000383673.5	NP_000787.2
DRD3	NM_001282563.2	c.1130C>T	p.Ala377Val	missense_variant	Exon 8 of 8		NP_001269492.1
DRD3	NM_001290809.1	c.1130C>T	p.Ala377Val	missense_variant	Exon 8 of 8		NP_001277738.1
DRD3	NM_033663.6	c.1031C>T	p.Ala344Val	missense_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.1130C>T	p.Ala377Val	missense_variant	Exon 7 of 7	1	NM_000796.6	ENSP00000373169.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251208 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

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: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	26
DANN	Pathogenic	1.0
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	.;.;D;D
M_CAP	Benign	0.064	D
MetaRNN	Pathogenic	0.91	D;D;D;D
MetaSVM	Benign	-0.70	T
PhyloP100		10
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-2.8	D;D;D;D
REVEL	Uncertain	0.56
Sift	Benign	0.032	D;D;D;D
Sift4G	Uncertain	0.028	D;D;D;D
Polyphen		0.99	.;.;D;.
Vest4		0.89
MutPred		0.78		Loss of glycosylation at S376 (P = 0.1256);Loss of glycosylation at S376 (P = 0.1256);.;Loss of glycosylation at S376 (P = 0.1256);
MVP		0.95
MPC		1.2
ClinPred		0.99	D
GERP RS		5.4
gMVP		0.77
Mutation Taster		=7/93	disease causing

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: rs769658489; hg19: chr3-113847636;