chrX-151180098-A-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_004224.3(GPR50):ā€‹c.515A>Gā€‹(p.Asp172Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000133 in 1,207,529 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000018 ( 0 hom., 0 hem., cov: 23)
Exomes š‘“: 0.000013 ( 0 hom. 5 hem. )

Consequence

GPR50
NM_004224.3 missense

Scores

5
10
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.39
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.811
BS2
High Hemizygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GPR50NM_004224.3 linkuse as main transcriptc.515A>G p.Asp172Gly missense_variant 2/2 ENST00000218316.4
GPR50XM_011531216.3 linkuse as main transcriptc.1+6A>G splice_donor_region_variant, intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GPR50ENST00000218316.4 linkuse as main transcriptc.515A>G p.Asp172Gly missense_variant 2/21 NM_004224.3 P1

Frequencies

GnomAD3 genomes
AF:
0.0000180
AC:
2
AN:
110891
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
33175
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000378
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000553
AC:
1
AN:
180922
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
66728
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:
0.0000123
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000128
AC:
14
AN:
1096638
Hom.:
0
Cov.:
33
AF XY:
0.0000138
AC XY:
5
AN XY:
362120
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:
0.0000155
Gnomad4 OTH exome
AF:
0.0000217
GnomAD4 genome
AF:
0.0000180
AC:
2
AN:
110891
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
33175
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000378
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000346
AC:
1

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 submitterclinical testingAmbry GeneticsMay 17, 2023The c.515A>G (p.D172G) alteration is located in exon 2 (coding exon 2) of the GPR50 gene. This alteration results from a A to G substitution at nucleotide position 515, causing the aspartic acid (D) at amino acid position 172 to be replaced by a glycine (G). 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
Pathogenic
0.95
BayesDel_addAF
Uncertain
0.071
D
BayesDel_noAF
Benign
-0.14
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.58
D
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.92
D
M_CAP
Uncertain
0.16
D
MetaRNN
Pathogenic
0.81
D
MetaSVM
Uncertain
0.30
D
MutationAssessor
Pathogenic
3.0
M
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.55
T
PROVEAN
Pathogenic
-6.8
D
REVEL
Uncertain
0.54
Sift
Uncertain
0.011
D
Sift4G
Uncertain
0.010
D
Polyphen
0.21
B
Vest4
0.64
MutPred
0.60
Loss of stability (P = 0.178);
MVP
0.95
MPC
0.48
ClinPred
0.96
D
GERP RS
4.3
Varity_R
0.78
gMVP
0.87

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.

Other links and lift over

dbSNP: rs755414121; hg19: chrX-150348570; API