chr4-9782660-G-T

Variant names:

• chr4-9782660-G-T
• NM_000798.5:c.631G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000798.5(DRD5):​c.631G>T​(p.Asp211Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DRD5 NM_000798.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.07

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=0.18205965).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD5	NM_000798.5	c.631G>T	p.Asp211Tyr	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.631G>T	p.Asp211Tyr	missense_variant	Exon 1 of 1	6	NM_000798.5	ENSP00000306129.2
SLC2A9	ENST00000503803.5	n.386-2595C>A		intron_variant	Intron 3 of 3	3
SLC2A9	ENST00000508585.5	n.182-11291C>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461662 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727140

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	14
DANN	Benign	0.91
DEOGEN2	Benign	0.073	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.090	N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.15
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.026	D
Polyphen		0.51	P
Vest4		0.20
MutPred		0.57		Loss of disorder (P = 0.0434);
MVP		0.46
MPC		0.45
ClinPred		0.38	T
GERP RS		2.8
Varity_R		0.090
gMVP		0.63

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-9784284;