4-9782361-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_000798.5(DRD5):​c.332C>A​(p.Ala111Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,614,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DRD5
NM_000798.5 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.66

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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.30762482).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DRD5NM_000798.5 linkc.332C>A p.Ala111Glu 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.332C>A p.Ala111Glu missense_variant Exon 1 of 1 6 NM_000798.5 ENSP00000306129.2 P21918
SLC2A9ENST00000503803.5 linkn.386-2296G>T intron_variant Intron 3 of 3 3
SLC2A9ENST00000508585.5 linkn.182-10992G>T intron_variant Intron 1 of 1 3

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152234
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:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.00000398
AC:
1
AN:
251030
AF XY:
0.00000737
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 FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461660
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727140
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33470
American (AMR)
AF:
0.00
AC:
0
AN:
44716
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26132
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.0000116
AC:
1
AN:
86250
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53414
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5760
European-Non Finnish (NFE)
AF:
8.99e-7
AC:
1
AN:
1111840
Other (OTH)
AF:
0.00
AC:
0
AN:
60378
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.450
Heterozygous variant carriers
0
0
1
1
2
2
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:
0.00000656
AC:
1
AN:
152352
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
74500
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41590
American (AMR)
AF:
0.00
AC:
0
AN:
15312
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.000193
AC:
1
AN:
5182
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4826
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10622
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68030
Other (OTH)
AF:
0.00
AC:
0
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 01, 2023
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.332C>A (p.A111E) alteration is located in exon 1 (coding exon 1) of the DRD5 gene. This alteration results from a C to A substitution at nucleotide position 332, causing the alanine (A) at amino acid position 111 to be replaced by a glutamic acid (E). 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
0.15
BayesDel_addAF
Uncertain
0.029
T
BayesDel_noAF
Benign
-0.10
CADD
Benign
22
DANN
Uncertain
0.98
DEOGEN2
Benign
0.17
T
Eigen
Benign
0.13
Eigen_PC
Benign
0.17
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.61
T
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.31
T
MetaSVM
Benign
-0.62
T
MutationAssessor
Benign
1.3
L
PhyloP100
3.7
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
-2.0
N
REVEL
Uncertain
0.49
Sift
Benign
0.32
T
Sift4G
Benign
0.27
T
Polyphen
0.88
P
Vest4
0.57
MVP
0.51
MPC
0.59
ClinPred
0.82
D
GERP RS
4.1
Varity_R
0.42
gMVP
0.72
Mutation Taster
=64/36
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: rs201570391; hg19: chr4-9783985; API