3-114128436-T-A

Position:

• chr3-114128436-T-A

Variant summary

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

The ENST00000383673.5(DRD3):​c.*280A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 152,156 control chromosomes in the GnomAD database, including 7,920 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 0.30 (7920 hom., cov: 32)
• Consequence: DRD3 ENST00000383673.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.133

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=-0.66).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DRD3	NM_000796.6	c.*280A>T		3_prime_UTR_variant	7/7	ENST00000383673.5	NP_000787.2
DRD3	NM_033663.6	c.*280A>T		3_prime_UTR_variant	8/8		NP_387512.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRD3	ENST00000383673.5	c.*280A>T		3_prime_UTR_variant	7/7	1	NM_000796.6	ENSP00000373169	P1
DRD3	ENST00000698213.1	c.*787A>T		3_prime_UTR_variant, NMD_transcript_variant	8/8			ENSP00000513607

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45234 AN: 152038 Hom.: 7921 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.297 AC: 45234 AN: 152156 Hom.: 7920 Cov.: 32 AF XY: 0.294 AC XY: 21853 AN XY: 74376

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.270

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.351

Gnomad4 SAS AF: 0.275

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.403

Gnomad4 OTH AF: 0.293

Alfa AF: 0.353 Hom.: 1330

Bravo AF: 0.284

Asia WGS AF: 0.299 AC: 1042 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	9.5
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3732790; hg19: chr3-113847283;