3-114128842-G-T

Variant names:

• chr3-114128842-G-T
• NM_000796.6:c.1077C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000796.6(DRD3):​c.1077C>A​(p.His359Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. H359H) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: DRD3 NM_000796.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24495691).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD3	NM_000796.6	c.1077C>A	p.His359Gln	missense_variant	Exon 7 of 7	ENST00000383673.5	NP_000787.2
DRD3	NM_001282563.2	c.1077C>A	p.His359Gln	missense_variant	Exon 8 of 8		NP_001269492.1
DRD3	NM_001290809.1	c.1077C>A	p.His359Gln	missense_variant	Exon 8 of 8		NP_001277738.1
DRD3	NM_033663.6	c.978C>A	p.His326Gln	missense_variant	Exon 8 of 8		NP_387512.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRD3	ENST00000383673.5	c.1077C>A	p.His359Gln	missense_variant	Exon 7 of 7	1	NM_000796.6	ENSP00000373169.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461656 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727136

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	1.3
DANN	Benign	0.96
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.78	.;.;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.24	T;T;T;T
MetaSVM	Benign	-0.93	T
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-2.8	D;D;D;D
REVEL	Benign	0.11
Sift	Benign	0.14	T;T;T;T
Sift4G	Benign	0.61	T;T;T;T
Polyphen		0.030	.;.;B;.
Vest4		0.44
MutPred		0.47		Loss of glycosylation at T357 (P = 0.0643);Loss of glycosylation at T357 (P = 0.0643);.;Loss of glycosylation at T357 (P = 0.0643);
MVP		0.83
MPC		0.46
ClinPred		0.54	D
GERP RS		-0.41
gMVP		0.64

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: chr3-113847689;