rs571899363

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_000797.4(DRD4):ā€‹c.187C>Gā€‹(p.Arg63Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,396,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 7.2e-7 ( 0 hom. )

Consequence

DRD4
NM_000797.4 missense

Scores

4
5
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.35
Variant links:
Genes affected
DRD4 (HGNC:3025): (dopamine receptor D4) This gene encodes the D4 subtype of the dopamine receptor. The D4 subtype is a G-protein coupled receptor which inhibits adenylyl cyclase. It is a target for drugs which treat schizophrenia and Parkinson disease. Mutations in this gene have been associated with various behavioral phenotypes, including autonomic nervous system dysfunction, attention deficit/hyperactivity disorder, and the personality trait of novelty seeking. This gene contains a polymorphic number (2-10 copies) of tandem 48 nt repeats; the sequence shown contains four repeats. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.81

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DRD4NM_000797.4 linkc.187C>G p.Arg63Gly missense_variant Exon 1 of 4 ENST00000176183.6 NP_000788.2 P21917

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DRD4ENST00000176183.6 linkc.187C>G p.Arg63Gly missense_variant Exon 1 of 4 1 NM_000797.4 ENSP00000176183.5 P21917

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000650
AC:
1
AN:
153754
Hom.:
0
AF XY:
0.0000120
AC XY:
1
AN XY:
83106
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000160
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
7.16e-7
AC:
1
AN:
1396110
Hom.:
0
Cov.:
32
AF XY:
0.00000145
AC XY:
1
AN XY:
690092
show subpopulations
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:
9.22e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000434
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.23
BayesDel_addAF
Benign
-0.091
T
BayesDel_noAF
Benign
-0.36
CADD
Uncertain
25
DANN
Uncertain
0.98
Eigen
Uncertain
0.29
Eigen_PC
Benign
0.20
FATHMM_MKL
Uncertain
0.91
D
M_CAP
Pathogenic
0.42
D
MetaRNN
Pathogenic
0.81
D
MetaSVM
Benign
-0.76
T
PrimateAI
Pathogenic
0.86
D
PROVEAN
Pathogenic
-4.5
D
REVEL
Benign
0.26
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.0020
D
Vest4
0.57
MutPred
0.72
Gain of glycosylation at T61 (P = 0.1002);
MVP
0.73
MPC
0.36
ClinPred
0.91
D
GERP RS
2.4
gMVP
0.49

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs571899363; hg19: chr11-637491; API