3-114131231-A-C

Variant names:

• chr3-114131231-A-C
• NM_000796.6:c.893T>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000796.6(DRD3):​c.893T>G​(p.Val298Gly) 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 benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DRD3 NM_000796.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.41

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4224629).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD3	NM_000796.6	c.893T>G	p.Val298Gly	missense_variant	Exon 6 of 7	ENST00000383673.5	NP_000787.2
DRD3	NM_001282563.2	c.893T>G	p.Val298Gly	missense_variant	Exon 7 of 8		NP_001269492.1
DRD3	NM_001290809.1	c.893T>G	p.Val298Gly	missense_variant	Exon 7 of 8		NP_001277738.1
DRD3	NM_033663.6	c.859+34T>G		intron_variant	Intron 6 of 7		NP_387512.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRD3	ENST00000383673.5	c.893T>G	p.Val298Gly	missense_variant	Exon 6 of 7	1	NM_000796.6	ENSP00000373169.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 05, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.893T>G (p.V298G) alteration is located in exon 6 (coding exon 5) of the DRD3 gene. This alteration results from a T to G substitution at nucleotide position 893, causing the valine (V) at amino acid position 298 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	26
DANN	Uncertain	0.98
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.56	.;.;T
M_CAP	Benign	0.080	D
MetaRNN	Benign	0.42	T;T;T
MetaSVM	Benign	-0.51	T
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.8	D;D;D
REVEL	Uncertain	0.48
Sift	Benign	0.071	T;T;T
Sift4G	Benign	0.42	T;T;T
Vest4		0.56
MutPred		0.46		Loss of stability (P = 0.0013);Loss of stability (P = 0.0013);Loss of stability (P = 0.0013);
MVP		0.92
MPC		1.3
ClinPred		0.96	D
GERP RS		5.5
gMVP		0.79

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-113850078;