rs62620754

chrX-151181061-G-A

Variant summary

Our verdict is Benign. Variant got -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. 13/19 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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
GPR50	NM_004224.3	c.1478G>A	p.Ser493Asn	missense_variant	2/2	ENST00000218316.4
GPR50	XM_011531216.3	c.737G>A	p.Ser246Asn	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR50	ENST00000218316.4	c.1478G>A	p.Ser493Asn	missense_variant	2/2	1	NM_004224.3	P1

Frequencies

GnomAD3 genomes AF: 0.0965 AC: 10634 AN: 110177 Hom.: 420 Cov.: 22 AF XY: 0.0886 AC XY: 2878 AN XY: 32497

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

GnomAD3 exomes AF: 0.0793 AC: 14359 AN: 181112 Hom.: 396 AF XY: 0.0792 AC XY: 5309 AN XY: 67072

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 SAS exome AF: 0.0614

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

Gnomad4 AFR exome AF: 0.144

Gnomad4 AMR exome AF: 0.0435

Gnomad4 ASJ exome AF: 0.0882

Gnomad4 EAS exome AF: 0.0648

Gnomad4 SAS exome AF: 0.0618

Gnomad4 FIN exome AF: 0.0726

Gnomad4 NFE exome AF: 0.0816

Gnomad4 OTH exome AF: 0.0922

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

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.0628

Gnomad4 ASJ AF: 0.0983

Gnomad4 EAS AF: 0.0637

Gnomad4 SAS AF: 0.0451

Gnomad4 FIN AF: 0.0635

Gnomad4 NFE AF: 0.0868

Gnomad4 OTH AF: 0.0961

Alfa AF: 0.0928 Hom.: 1031

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
MutationTaster	Benign	1.0	P
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

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

LitVar

Other links and lift over

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