chrX-151176819-G-C

Variant summary

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

The NM_004224.3(GPR50):ā€‹c.98G>Cā€‹(p.Cys33Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000667 in 1,199,941 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000090 ( 0 hom., 1 hem., cov: 23)
Exomes š‘“: 0.0000064 ( 0 hom. 4 hem. )

Consequence

GPR50
NM_004224.3 missense

Scores

2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.37
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-AS1 (HGNC:40259): (GPR50 antisense RNA 1)

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=0.14344054).
BS2
High Hemizygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GPR50NM_004224.3 linkuse as main transcriptc.98G>C p.Cys33Ser missense_variant 1/2 ENST00000218316.4
GPR50-AS1NR_135300.1 linkuse as main transcriptn.517C>G non_coding_transcript_exon_variant 2/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GPR50ENST00000218316.4 linkuse as main transcriptc.98G>C p.Cys33Ser missense_variant 1/21 NM_004224.3 P1
GPR50-AS1ENST00000454196.1 linkuse as main transcriptn.517C>G non_coding_transcript_exon_variant 2/32

Frequencies

GnomAD3 genomes
AF:
0.00000901
AC:
1
AN:
110973
Hom.:
0
Cov.:
23
AF XY:
0.0000301
AC XY:
1
AN XY:
33213
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000946
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000111
AC:
2
AN:
180445
Hom.:
0
AF XY:
0.0000151
AC XY:
1
AN XY:
66373
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000370
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:
0.000227
GnomAD4 exome
AF:
0.00000643
AC:
7
AN:
1088968
Hom.:
0
Cov.:
28
AF XY:
0.0000113
AC XY:
4
AN XY:
354922
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000569
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:
0.00000360
Gnomad4 OTH exome
AF:
0.0000437
GnomAD4 genome
AF:
0.00000901
AC:
1
AN:
110973
Hom.:
0
Cov.:
23
AF XY:
0.0000301
AC XY:
1
AN XY:
33213
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000946
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000793
ExAC
AF:
0.0000165
AC:
2

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 GeneticsJun 23, 2023The c.98G>C (p.C33S) alteration is located in exon 1 (coding exon 1) of the GPR50 gene. This alteration results from a G to C substitution at nucleotide position 98, causing the cysteine (C) at amino acid position 33 to be replaced by a serine (S). 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
0.12
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.71
CADD
Benign
15
DANN
Benign
0.79
DEOGEN2
Benign
0.054
T
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.52
T
M_CAP
Benign
0.0061
T
MetaRNN
Benign
0.14
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.46
N
MutationTaster
Benign
0.85
D
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-0.60
N
REVEL
Benign
0.035
Sift
Benign
0.12
T
Sift4G
Benign
0.18
T
Polyphen
0.0010
B
Vest4
0.36
MutPred
0.45
Loss of catalytic residue at M31 (P = 0.1022);
MVP
0.64
MPC
0.18
ClinPred
0.052
T
GERP RS
2.3
Varity_R
0.10
gMVP
0.58

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs751230928; hg19: chrX-150345291; API