rs139341493

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr3-114128872-A-C
• chr3-114128872-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM1 PM2 PP3

The NM_000796.6(DRD3):​c.1047T>G​(p.His349Gln) variant causes a missense change involving the alteration of a non-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. Synonymous variant affecting the same amino acid position (i.e. H349H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DRD3 NM_000796.6 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 5 ACMG points.

• PM1: In a binding_site (size 0) in uniprot entity DRD3_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD3	NM_000796.6	c.1047T>G	p.His349Gln	missense_variant	Exon 7 of 7	ENST00000383673.5	NP_000787.2
DRD3	NM_001282563.2	c.1047T>G	p.His349Gln	missense_variant	Exon 8 of 8		NP_001269492.1
DRD3	NM_001290809.1	c.1047T>G	p.His349Gln	missense_variant	Exon 8 of 8		NP_001277738.1
DRD3	NM_033663.6	c.948T>G	p.His316Gln	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.1047T>G	p.His349Gln	missense_variant	Exon 7 of 7	1	NM_000796.6	ENSP00000373169.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Benign	23
DANN	Uncertain	0.99
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.32
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Pathogenic	0.98	.;.;D;D
M_CAP	Benign	0.084	D
MetaRNN	Pathogenic	0.81	D;D;D;D
MetaSVM	Benign	-0.50	T
PhyloP100		0.85
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-6.0	D;D;D;D
REVEL	Uncertain	0.49
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Uncertain	0.0030	D;D;D;D
Polyphen		0.24	.;.;B;.
Vest4		0.90
MutPred		0.58		Loss of catalytic residue at L351 (P = 0.0674);Loss of catalytic residue at L351 (P = 0.0674);.;Loss of catalytic residue at L351 (P = 0.0674);
MVP		0.90
MPC		1.2
ClinPred		1.0	D
GERP RS		-1.8
gMVP		0.82
Mutation Taster		=36/64	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.74		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.74		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs139341493; hg19: chr3-113847719;