chr4-9782361-C-A

Variant names:

• chr4-9782361-C-A
• rs201570391
• NM_000798.5:c.332C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.66
• Publications: 0 publications found

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: AR, AD, SD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
• hereditary renal hypouricemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000798.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD5	NM_000798.5	MANE Select	c.332C>A	p.Ala111Glu	missense	Exon 1 of 1	NP_000789.1	P21918

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD5	ENST00000304374.4	TSL:6 MANE Select	c.332C>A	p.Ala111Glu	missense	Exon 1 of 1	ENSP00000306129.2	P21918
	DRD5	ENST00000888644.1		c.332C>A	p.Ala111Glu	missense	Exon 2 of 2	ENSP00000558703.1
	DRD5	ENST00000953045.1		c.332C>A	p.Ala111Glu	missense	Exon 2 of 2	ENSP00000623104.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152234 Hom.: 0 Cov.: 34

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

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

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

GnomAD4 genome AF: 0.00000656 AC: 1 AN: 152352 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 74500

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

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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

Other links and lift over

dbSNP: rs201570391; hg19: chr4-9783985;