Variant X-151180169-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_004224.3(GPR50):c.586C>A(p.His196Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000127 in 1,204,723 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 44 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00069 ( 0 hom., 23 hem., cov: 22)

Exomes 𝑓: 0.000070 ( 0 hom. 21 hem. )

Consequence

GPR50
NM_004224.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.86

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.111976326).

BS2

High Hemizygotes in GnomAd at 24 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR50	NM_004224.3 linkuse as main transcript	c.586C>A	p.His196Asn	missense_variant	2/2	ENST00000218316.4
GPR50	XM_011531216.3 linkuse as main transcript	c.1+77C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR50	ENST00000218316.4 linkuse as main transcript	c.586C>A	p.His196Asn	missense_variant	2/2	1	NM_004224.3	P1

Frequencies

GnomAD3 genomes

AF:

0.000699

AC:

AN:

111637

Hom.:

Cov.:

AF XY:

0.000711

AC XY:

AN XY:

33773

show subpopulations

Gnomad AFR

AF:

0.00238

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000189

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000380

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.000664

GnomAD3 exomes

AF:

0.000152

AC:

AN:

177542

Hom.:

AF XY:

0.000153

AC XY:

AN XY:

65352

show subpopulations

Gnomad AFR exome

AF:

0.00209

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.0000695

AC:

AN:

1093031

Hom.:

Cov.:

AF XY:

0.0000582

AC XY:

AN XY:

360799

show subpopulations

Gnomad4 AFR exome

AF:

0.00231

Gnomad4 AMR exome

AF:

0.0000568

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.000239

GnomAD4 genome

AF:

0.000689

AC:

AN:

111692

Hom.:

Cov.:

AF XY:

0.000680

AC XY:

AN XY:

33838

show subpopulations

Gnomad4 AFR

AF:

0.00238

Gnomad4 AMR

AF:

0.000189

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.000656

Alfa

AF:

0.0000395

Hom.:

Bravo

AF:

0.000861

ESP6500AA

AF:

0.00160

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000231

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 28, 2021

The c.586C>A (p.H196N) alteration is located in exon 2 (coding exon 2) of the GPR50 gene. This alteration results from a C to A substitution at nucleotide position 586, causing the histidine (H) at amino acid position 196 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.50

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.14

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Uncertain

0.57

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.72

M_CAP

Benign

0.065

MetaRNN

Benign

0.11

MetaSVM

Uncertain

0.034

MutationAssessor

Pathogenic

3.4

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.75

PROVEAN

Pathogenic

-7.0

REVEL

Uncertain

0.52

Sift

Benign

0.046

Sift4G

Pathogenic

0.0010

Polyphen

0.45

Vest4

0.74

MVP

0.92

MPC

0.49

ClinPred

0.26

GERP RS

4.3

Varity_R

0.80

gMVP

0.89

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

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