3-114128261-T-C

Variant names:

• chr3-114128261-T-C
• rs9817063
• NM_000796.6:c.*455A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000796.6(DRD3):​c.*455A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 151,960 control chromosomes in the GnomAD database, including 14,986 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.44 (14986 hom., cov: 32)
• Consequence: DRD3 NM_000796.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.239

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD3	NM_000796.6	c.*455A>G		3_prime_UTR_variant	Exon 7 of 7	ENST00000383673.5	NP_000787.2
DRD3	NM_033663.6	c.*455A>G		3_prime_UTR_variant	Exon 8 of 8		NP_387512.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRD3	ENST00000383673	c.*455A>G		3_prime_UTR_variant	Exon 7 of 7	1	NM_000796.6	ENSP00000373169.2
DRD3	ENST00000698213.1	n.*962A>G		non_coding_transcript_exon_variant	Exon 8 of 8			ENSP00000513607.1
DRD3	ENST00000698213.1	n.*962A>G		3_prime_UTR_variant	Exon 8 of 8			ENSP00000513607.1

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67072 AN: 151842 Hom.: 14976 Cov.: 32

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.528

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.426

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.442 AC: 67111 AN: 151960 Hom.: 14986 Cov.: 32 AF XY: 0.442 AC XY: 32813 AN XY: 74292

Gnomad4 AFR AF: 0.373

Gnomad4 AMR AF: 0.427

Gnomad4 ASJ AF: 0.390

Gnomad4 EAS AF: 0.450

Gnomad4 SAS AF: 0.447

Gnomad4 FIN AF: 0.528

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.431

Alfa AF: 0.467 Hom.: 28462

Bravo AF: 0.434

Asia WGS AF: 0.471 AC: 1637 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.0
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9817063; hg19: chr3-113847108;