chrX-151176900-G-A

Variant names:

• chrX-151176900-G-A
• rs375887607
• NM_004224.3:c.179G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_004224.3(GPR50):​c.179G>A​(p.Arg60Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000326 in 1,196,159 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 16 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R60W) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., 4 hem., cov: 22)
  • Exomes 𝑓: 0.000024 (0 hom. 12 hem.)
• Consequence: GPR50 NM_004224.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.79
• Publications: 5 publications found

Genes affected

GPR50 (HGNC:4506): (G protein-coupled receptor 50) This gene product belongs to the G-protein coupled receptor 1 family. Even though this protein shares similarity with the melatonin receptors, it does not bind melatonin, however, it inhibits melatonin receptor 1A function through heterodimerization. Polymorphic variants of this gene have been associated with bipolar affective disorder in women. [provided by RefSeq, Jan 2010]

GPR50-AS1 (HGNC:40259): (GPR50 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05799541).
• BS2: High Hemizygotes in GnomAd4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004224.3. 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
	GPR50	NM_004224.3	MANE Select	c.179G>A	p.Arg60Gln	missense	Exon 1 of 2	NP_004215.2	Q13585
	GPR50-AS1	NR_135300.1		n.461-25C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR50	ENST00000218316.4	TSL:1 MANE Select	c.179G>A	p.Arg60Gln	missense	Exon 1 of 2	ENSP00000218316.3	Q13585
	GPR50-AS1	ENST00000454196.1	TSL:2	n.461-25C>T		intron	N/A
	GPR50-AS1	ENST00000835194.1		n.440+477C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000117 AC: 13 AN: 111387 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.0117

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000943

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000233 AC: 4 AN: 172009 AF XY: 0.0000341

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: 0.0000387

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000240 AC: 26 AN: 1084772 Hom.: 0 Cov.: 27 AF XY: 0.0000342 AC XY: 12 AN XY: 350982

African (AFR) AF: 0.00 AC: 0 AN: 26070

American (AMR) AF: 0.00 AC: 0 AN: 34714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19008

East Asian (EAS) AF: 0.00 AC: 0 AN: 29986

South Asian (SAS) AF: 0.0000947 AC: 5 AN: 52799

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40411

Middle Eastern (MID) AF: 0.000493 AC: 2 AN: 4056

European-Non Finnish (NFE) AF: 0.0000204 AC: 17 AN: 832107

Other (OTH) AF: 0.0000438 AC: 2 AN: 45621

GnomAD4 genome AF: 0.000117 AC: 13 AN: 111387 Hom.: 0 Cov.: 22 AF XY: 0.000119 AC XY: 4 AN XY: 33583

African (AFR) AF: 0.00 AC: 0 AN: 30533

American (AMR) AF: 0.00 AC: 0 AN: 10640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2650

East Asian (EAS) AF: 0.00 AC: 0 AN: 3534

South Asian (SAS) AF: 0.00 AC: 0 AN: 2597

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6002

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.0000943 AC: 5 AN: 53012

Other (OTH) AF: 0.00 AC: 0 AN: 1496

Alfa AF: 0.000270 Hom.: 1

Bravo AF: 0.000189

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000156 AC: 1

ExAC AF: 0.0000414 AC: 5

ClinVar

ClinVar submissions as Germline

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	0.092
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.46	T
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.8	L
PhyloP100		3.8
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.27
Sift	Benign	0.099	T
Sift4G	Benign	0.083	T
Polyphen		0.61	P
Vest4		0.32
MVP		0.59
MPC		0.22
ClinPred		0.25	T
GERP RS		3.5
PromoterAI		-0.069	Neutral
Varity_R		0.12
gMVP		0.80
Mutation Taster		=93/7	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: rs375887607; hg19: chrX-150345372; COSMIC: COSV54438033;