NM_000798.5:c.186C>T

Variant names:

• chr4-9782215-C-T
• NM_000798.5:c.186C>T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_000798.5(DRD5):​c.186C>T​(p.Cys62Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,459,518 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 0.0000041 (0 hom.)
• Consequence: DRD5 NM_000798.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.838

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 Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP7: Synonymous conserved (PhyloP=-0.838 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD5	NM_000798.5	c.186C>T	p.Cys62Cys	synonymous_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.186C>T	p.Cys62Cys	synonymous_variant	Exon 1 of 1	6	NM_000798.5	ENSP00000306129.2
SLC2A9	ENST00000503803.5	n.386-2150G>A		intron_variant	Intron 3 of 3	3
SLC2A9	ENST00000508585.5	n.182-10846G>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1459518 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 725934

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: 0.00000450

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	2.4
DANN	Benign	0.89

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-9783839; COSMIC: COSV58578419;