chr4-9782262-T-G

Variant summary

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

The NM_000798.5(DRD5):​c.233T>G​(p.Val78Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000297 in 1,613,734 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

DRD5
NM_000798.5 missense

Scores

1
11
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.56

Publications

0 publications found
Variant links:
Genes affected
DRD5 (HGNC:3026): (dopamine receptor D5) This gene encodes the D5 subtype of the dopamine receptor. The D5 subtype is a G-protein coupled receptor which stimulates adenylyl cyclase. This receptor is expressed in neurons in the limbic regions of the brain. It has a 10-fold higher affinity for dopamine than the D1 subtype. Pseudogenes related to this gene reside on chromosomes 1 and 2. [provided by RefSeq, Jul 2008]
SLC2A9 (HGNC:13446): (solute carrier family 2 member 9) This gene encodes a member of the SLC2A facilitative glucose transporter family. Members of this family play a significant role in maintaining glucose homeostasis. The encoded protein may play a role in the development and survival of chondrocytes in cartilage matrices. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]
SLC2A9 Gene-Disease associations (from GenCC):
  • hypouricemia, renal, 2
    Inheritance: AD, AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
  • hereditary renal hypouricemia
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DRD5NM_000798.5 linkc.233T>G p.Val78Gly missense_variant Exon 1 of 1 ENST00000304374.4 NP_000789.1 P21918

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DRD5ENST00000304374.4 linkc.233T>G p.Val78Gly missense_variant Exon 1 of 1 6 NM_000798.5 ENSP00000306129.2 P21918
SLC2A9ENST00000503803.5 linkn.386-2197A>C intron_variant Intron 3 of 3 3
SLC2A9ENST00000508585.5 linkn.182-10893A>C intron_variant Intron 1 of 1 3

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152216
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000941
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000717
AC:
18
AN:
250986
AF XY:
0.0000884
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.000141
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000301
AC:
44
AN:
1461518
Hom.:
0
Cov.:
31
AF XY:
0.0000289
AC XY:
21
AN XY:
727068
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33472
American (AMR)
AF:
0.0000224
AC:
1
AN:
44714
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26132
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86236
European-Finnish (FIN)
AF:
0.0000187
AC:
1
AN:
53400
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5654
European-Non Finnish (NFE)
AF:
0.0000378
AC:
42
AN:
1111850
Other (OTH)
AF:
0.00
AC:
0
AN:
60360
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
4
8
11
15
19
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152216
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
74374
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41464
American (AMR)
AF:
0.00
AC:
0
AN:
15292
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3468
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5180
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4834
European-Finnish (FIN)
AF:
0.0000941
AC:
1
AN:
10630
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000441
AC:
3
AN:
68028
Other (OTH)
AF:
0.00
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.488
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000189
ExAC
AF:
0.0000988
AC:
12
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 31, 2022
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.233T>G (p.V78G) alteration is located in exon 1 (coding exon 1) of the DRD5 gene. This alteration results from a T to G substitution at nucleotide position 233, causing the valine (V) at amino acid position 78 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
Benign
0.19
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.13
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.33
T
Eigen
Uncertain
0.47
Eigen_PC
Uncertain
0.40
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.90
D
M_CAP
Benign
0.044
D
MetaRNN
Uncertain
0.55
D
MetaSVM
Uncertain
-0.051
T
MutationAssessor
Uncertain
2.1
M
PhyloP100
4.6
PrimateAI
Uncertain
0.50
T
PROVEAN
Uncertain
-3.1
D
REVEL
Uncertain
0.63
Sift
Uncertain
0.0060
D
Sift4G
Benign
0.065
T
Polyphen
0.99
D
Vest4
0.27
MutPred
0.69
Loss of stability (P = 0.0138);
MVP
0.60
MPC
0.59
ClinPred
0.62
D
GERP RS
4.0
Varity_R
0.57
gMVP
0.75
Mutation Taster
=77/23
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

Publications

Other links and lift over

dbSNP: rs774529086; hg19: chr4-9783886; API