3-114139416-G-T

Variant names:

• chr3-114139416-G-T
• rs9828046
• NM_000796.6:c.723+84C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000796.6(DRD3):​c.723+84C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000169 in 1,182,830 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: DRD3 NM_000796.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.56
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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.723+84C>A		intron	N/A	NP_000787.2	X5D2G4
	DRD3	NM_001282563.2		c.723+84C>A		intron	N/A	NP_001269492.1	P35462-1
	DRD3	NM_001290809.1		c.723+84C>A		intron	N/A	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.723+84C>A		intron	N/A	ENSP00000373169.2	P35462-1
	DRD3	ENST00000467632.5	TSL:1	c.723+84C>A		intron	N/A	ENSP00000420662.1	P35462-1
	DRD3	ENST00000460779.5	TSL:2	c.723+84C>A		intron	N/A	ENSP00000419402.1	P35462-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000169 AC: 2 AN: 1182830 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 582442

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 27246

American (AMR) AF: 0.00 AC: 0 AN: 29000

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18386

East Asian (EAS) AF: 0.00 AC: 0 AN: 36864

South Asian (SAS) AF: 0.00 AC: 0 AN: 54920

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46990

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3320

European-Non Finnish (NFE) AF: 0.00000218 AC: 2 AN: 916766

Other (OTH) AF: 0.00 AC: 0 AN: 49338

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.3
DANN	Benign	0.48
PhyloP100		1.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs9828046; hg19: chr3-113858263;