chr4-9782153-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000798.5(DRD5):c.124G>A(p.Val42Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000021 in 1,427,918 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

DRD5
NM_000798.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.30

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]

DRD5 links:

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

SLC2A9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.16811419).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD5	NM_000798.5 link	c.124G>A	p.Val42Ile	missense_variant	Exon 1 of 1	ENST00000304374.4	NP_000789.1	P21918

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DRD5	ENST00000304374.4 link	c.124G>A	p.Val42Ile	missense_variant	Exon 1 of 1	6	NM_000798.5	ENSP00000306129.2	P21918
SLC2A9	ENST00000503803.5 link	n.386-2088C>T		intron_variant	Intron 3 of 3	3
SLC2A9	ENST00000508585.5 link	n.182-10784C>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000470

AC:

AN:

212760

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000585

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000210

AC:

AN:

1427918

Hom.:

Cov.:

AF XY:

0.00000283

AC XY:

AN XY:

706486

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32974

American (AMR)

AF:

0.00

AC:

AN:

42664

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23820

East Asian (EAS)

AF:

0.0000256

AC:

AN:

39040

South Asian (SAS)

AF:

0.00

AC:

AN:

79976

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50922

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4672

European-Non Finnish (NFE)

AF:

0.00000183

AC:

AN:

1095092

Other (OTH)

AF:

0.00

AC:

AN:

58758

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 27, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.124G>A (p.V42I) alteration is located in exon 1 (coding exon 1) of the DRD5 gene. This alteration results from a G to A substitution at nucleotide position 124, causing the valine (V) at amino acid position 42 to be replaced by an isoleucine (I). 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

0.089

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.049

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.15

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.58

M_CAP

Benign

0.0037

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

3.3

PrimateAI

Uncertain

0.70

PROVEAN

Benign

0.10

REVEL

Benign

0.10

Sift

Benign

0.31

Sift4G

Benign

0.48

Polyphen

0.70

Vest4

0.21

MutPred

0.33

Loss of catalytic residue at V42 (P = 0.0024);

MVP

0.17

MPC

0.34

ClinPred

0.22

GERP RS

3.8

Varity_R

0.10

gMVP

0.31

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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chr4-9782153-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over