3-114131321-C-G

Variant names:

• chr3-114131321-C-G
• NM_000796.6:c.803G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000796.6(DRD3):​c.803G>C​(p.Gly268Ala) 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 benign outcome for this variant. 16/20 in silico tools predict 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: 0.696
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11264101).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD3	NM_000796.6	c.803G>C	p.Gly268Ala	missense_variant	Exon 6 of 7	ENST00000383673.5	NP_000787.2
DRD3	NM_001282563.2	c.803G>C	p.Gly268Ala	missense_variant	Exon 7 of 8		NP_001269492.1
DRD3	NM_001290809.1	c.803G>C	p.Gly268Ala	missense_variant	Exon 7 of 8		NP_001277738.1
DRD3	NM_033663.6	c.803G>C	p.Gly268Ala	missense_variant	Exon 6 of 8		NP_387512.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRD3	ENST00000383673.5	c.803G>C	p.Gly268Ala	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

Jan 19, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.803G>C (p.G268A) alteration is located in exon 6 (coding exon 5) of the DRD3 gene. This alteration results from a G to C substitution at nucleotide position 803, causing the glycine (G) at amino acid position 268 to be replaced by an alanine (A). 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	Benign	0.073
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	14
DANN	Benign	0.79
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.42
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.76	.;.;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-0.99	T
PhyloP100		0.70
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.65	N;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.41	T;T;T;T
Sift4G	Benign	0.69	T;T;T;T
Polyphen		0.017	.;.;B;.
Vest4		0.18
MutPred		0.49		Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP		0.89
MPC		0.40
ClinPred		0.096	T
GERP RS		3.8
gMVP		0.28
Mutation Taster		=85/15	polymorphism

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

Other links and lift over

hg19: chr3-113850168;