4-9782153-G-A

Variant names:

• chr4-9782153-G-A
• rs1296767794
• NM_000798.5:c.124G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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. 13/21 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.30

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]

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=0.16811419).

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.00000470 AC: 1 AN: 212760 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 114532

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 SAS 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: 0.00000210 AC: 3 AN: 1427918 Hom.: 0 Cov.: 30 AF XY: 0.00000283 AC XY: 2 AN XY: 706486

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000256

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000183

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

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	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.049	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	0.10	N
REVEL	Benign	0.10
Sift	Benign	0.31	T
Sift4G	Benign	0.48	T
Polyphen		0.70	P
Vest4		0.21
MutPred		0.33		Loss of catalytic residue at V42 (P = 0.0024);
MVP		0.17
MPC		0.34
ClinPred		0.22	T
GERP RS		3.8
Varity_R		0.10
gMVP		0.31

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

LitVar

Other links and lift over

dbSNP: rs1296767794; hg19: chr4-9783777;