Variant X-151176782-C-G 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.61C>G(p.Pro21Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000998 in 1,202,245 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 21)

Exomes 𝑓: 0.0000092 ( 0 hom. 3 hem. )

Consequence

GPR50
NM_004224.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.06

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:40259): (GPR50 antisense RNA 1)

GPR50-AS1 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=0.17538333).

BS2

High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR50	NM_004224.3 linkuse as main transcript	c.61C>G	p.Pro21Ala	missense_variant	1/2	ENST00000218316.4
GPR50-AS1	NR_135300.1 linkuse as main transcript	n.541+13G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR50	ENST00000218316.4 linkuse as main transcript	c.61C>G	p.Pro21Ala	missense_variant	1/2	1	NM_004224.3	P1
GPR50-AS1	ENST00000454196.1 linkuse as main transcript	n.541+13G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000181

AC:

AN:

110712

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32936

show subpopulations

Gnomad AFR

AF:

0.0000330

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000189

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000112

AC:

AN:

178741

Hom.:

AF XY:

0.0000154

AC XY:

AN XY:

64779

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000249

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000916

AC:

AN:

1091533

Hom.:

Cov.:

AF XY:

0.00000840

AC XY:

AN XY:

357261

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.0000218

GnomAD4 genome

AF:

0.0000181

AC:

AN:

110712

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32936

show subpopulations

Gnomad4 AFR

AF:

0.0000330

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000189

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000189

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000156

AC:

ExAC

AF:

0.0000166

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

Dec 21, 2023

The c.61C>G (p.P21A) alteration is located in exon 1 (coding exon 1) of the GPR50 gene. This alteration results from a C to G substitution at nucleotide position 61, causing the proline (P) at amino acid position 21 to be replaced by an alanine (A). 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

Benign

0.15

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.085

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.73

M_CAP

Benign

0.014

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

MutationTaster

Benign

0.99

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.7

REVEL

Benign

0.15

Sift

Uncertain

0.014

Sift4G

Uncertain

0.035

Polyphen

0.11

Vest4

0.49

MVP

0.56

MPC

0.18

ClinPred

0.14

GERP RS

4.2

Varity_R

0.098

gMVP

0.34

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