rs62620754

Variant names:

• chrX-151181061-G-A
• rs62620754
• NM_004224.3:c.1478G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004224.3(GPR50):​c.1478G>A​(p.Ser493Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0822 in 1,208,046 control chromosomes in the GnomAD database, including 3,041 homozygotes. There are 32,046 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 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: 𝑓 0.097 (420 hom., 2895 hem., cov: 22)
  • Exomes 𝑓: 0.081 (2621 hom. 29151 hem.)
• Consequence: GPR50 NM_004224.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.78
• Publications: 8 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015604496).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR50	NM_004224.3	c.1478G>A	p.Ser493Asn	missense_variant	Exon 2 of 2	ENST00000218316.4	NP_004215.2
GPR50	XM_011531216.3	c.737G>A	p.Ser246Asn	missense_variant	Exon 2 of 2		XP_011529518.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR50	ENST00000218316.4	c.1478G>A	p.Ser493Asn	missense_variant	Exon 2 of 2	1	NM_004224.3	ENSP00000218316.3

Frequencies

GnomAD3 genomes AF: 0.0965 AC: 10634 AN: 110177 Hom.: 420 Cov.: 22

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.0805

Gnomad AMR AF: 0.0629

Gnomad ASJ AF: 0.0983

Gnomad EAS AF: 0.0641

Gnomad SAS AF: 0.0450

Gnomad FIN AF: 0.0635

Gnomad MID AF: 0.100

Gnomad NFE AF: 0.0868

Gnomad OTH AF: 0.0973

GnomAD2 exomes AF: 0.0793 AC: 14359 AN: 181112 AF XY: 0.0792

Gnomad AFR exome AF: 0.143

Gnomad AMR exome AF: 0.0414

Gnomad ASJ exome AF: 0.0908

Gnomad EAS exome AF: 0.0698

Gnomad FIN exome AF: 0.0703

Gnomad NFE exome AF: 0.0879

Gnomad OTH exome AF: 0.0933

GnomAD4 exome AF: 0.0808 AC: 88711 AN: 1097810 Hom.: 2621 Cov.: 34 AF XY: 0.0802 AC XY: 29151 AN XY: 363324

African (AFR) AF: 0.144 AC: 3793 AN: 26386

American (AMR) AF: 0.0435 AC: 1530 AN: 35193

Ashkenazi Jewish (ASJ) AF: 0.0882 AC: 1709 AN: 19376

East Asian (EAS) AF: 0.0648 AC: 1958 AN: 30200

South Asian (SAS) AF: 0.0618 AC: 3346 AN: 54130

European-Finnish (FIN) AF: 0.0726 AC: 2940 AN: 40490

Middle Eastern (MID) AF: 0.122 AC: 505 AN: 4134

European-Non Finnish (NFE) AF: 0.0816 AC: 68682 AN: 841821

Other (OTH) AF: 0.0922 AC: 4248 AN: 46080

GnomAD4 genome AF: 0.0966 AC: 10649 AN: 110236 Hom.: 420 Cov.: 22 AF XY: 0.0889 AC XY: 2895 AN XY: 32564

African (AFR) AF: 0.140 AC: 4231 AN: 30217

American (AMR) AF: 0.0628 AC: 653 AN: 10390

Ashkenazi Jewish (ASJ) AF: 0.0983 AC: 259 AN: 2634

East Asian (EAS) AF: 0.0637 AC: 223 AN: 3499

South Asian (SAS) AF: 0.0451 AC: 114 AN: 2528

European-Finnish (FIN) AF: 0.0635 AC: 371 AN: 5838

Middle Eastern (MID) AF: 0.104 AC: 22 AN: 211

European-Non Finnish (NFE) AF: 0.0868 AC: 4579 AN: 52758

Other (OTH) AF: 0.0961 AC: 142 AN: 1478

Alfa AF: 0.103 Hom.: 1491

Bravo AF: 0.101

TwinsUK AF: 0.0715 AC: 265

ALSPAC AF: 0.0779 AC: 225

ESP6500AA AF: 0.134 AC: 490

ESP6500EA AF: 0.0846 AC: 558

ExAC AF: 0.0834 AC: 10105

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.070	T
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.64	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.8
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.18
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.16	T
Polyphen		0.062	B
Vest4		0.067
MPC		0.28
ClinPred		0.045	T
GERP RS		3.5
Varity_R		0.20
gMVP		0.17
Mutation Taster		=98/2	polymorphism (auto)

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: rs62620754; hg19: chrX-150349533; COSMIC: COSV99029151; COSMIC: COSV99029151;