Variant X-151176899-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 1P and 12B. PP3BP6_Very_StrongBS2

The NM_004224.3(GPR50):c.178C>T(p.Arg60Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000398 in 1,197,034 control chromosomes in the GnomAD database, including 1 homozygotes. There are 144 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., 4 hem., cov: 22)

Exomes 𝑓: 0.00042 ( 1 hom. 140 hem. )

Consequence

GPR50
NM_004224.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.35

Variant links:

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 links:

GPR50-AS1 (HGNC:):

GPR50-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.791

BP6

Variant X-151176899-C-T is Benign according to our data. Variant chrX-151176899-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1206241.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-151176899-C-T is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR50	NM_004224.3 linkuse as main transcript	c.178C>T	p.Arg60Trp	missense_variant	1/2	ENST00000218316.4	NP_004215.2	Q13585
GPR50-AS1	NR_135300.1 linkuse as main transcript	n.461-24G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR50	ENST00000218316.4 linkuse as main transcript	c.178C>T	p.Arg60Trp	missense_variant	1/2	1	NM_004224.3	ENSP00000218316.3		Q13585
GPR50-AS1	ENST00000454196.1 linkuse as main transcript	n.461-24G>A		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

111452

Hom.:

Cov.:

AF XY:

0.000119

AC XY:

AN XY:

33632

show subpopulations

Gnomad AFR

AF:

0.000131

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000833

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000226

Gnomad OTH

AF:

0.000668

GnomAD3 exomes

AF:

0.000301

AC:

AN:

172622

Hom.:

AF XY:

0.000321

AC XY:

AN XY:

59128

show subpopulations

Gnomad AFR exome

AF:

0.0000820

Gnomad AMR exome

AF:

0.0000765

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000764

Gnomad NFE exome

AF:

0.000476

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000418

AC:

454

AN:

1085582

Hom.:

Cov.:

AF XY:

0.000398

AC XY:

140

AN XY:

351700

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000863

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000378

Gnomad4 FIN exome

AF:

0.000693

Gnomad4 NFE exome

AF:

0.000491

Gnomad4 OTH exome

AF:

0.000241

GnomAD4 genome

AF:

0.000197

AC:

AN:

111452

Hom.:

Cov.:

AF XY:

0.000119

AC XY:

AN XY:

33632

show subpopulations

Gnomad4 AFR

AF:

0.000131

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000833

Gnomad4 NFE

AF:

0.000226

Gnomad4 OTH

AF:

0.000668

Alfa

AF:

0.000216

Hom.:

Bravo

AF:

0.000144

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000311

AC:

ExAC

AF:

0.000331

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2023	GPR50: BS2 -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.0079

BayesDel_noAF

Uncertain

0.080

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.57

FATHMM_MKL

Uncertain

0.84

LIST_S2

Pathogenic

0.98

M_CAP

Uncertain

0.092

MetaRNN

Pathogenic

0.79

MetaSVM

Uncertain

-0.18

MutationAssessor

Pathogenic

4.1

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-5.9

REVEL

Uncertain

0.40

Sift

Uncertain

0.0020

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.73

MVP

0.89

MPC

0.40

ClinPred

0.46

GERP RS

4.4

Varity_R

0.44

gMVP

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over