chrX-151176776-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004224.3(GPR50):​c.55C>T​(p.Pro19Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 22)
Exomes 𝑓: 9.2e-7 ( 0 hom. 1 hem. )
Failed GnomAD Quality Control

Consequence

GPR50
NM_004224.3 missense

Scores

3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.03
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.21875975).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GPR50NM_004224.3 linkuse as main transcriptc.55C>T p.Pro19Ser missense_variant 1/2 ENST00000218316.4
GPR50-AS1NR_135300.1 linkuse as main transcriptn.541+19G>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GPR50ENST00000218316.4 linkuse as main transcriptc.55C>T p.Pro19Ser missense_variant 1/21 NM_004224.3 P1
GPR50-AS1ENST00000454196.1 linkuse as main transcriptn.541+19G>A intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
9.16e-7
AC:
1
AN:
1091351
Hom.:
0
Cov.:
28
AF XY:
0.00000280
AC XY:
1
AN XY:
357283
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:
0.00000120
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
22

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 GeneticsSep 16, 2021The c.55C>T (p.P19S) alteration is located in exon 1 (coding exon 1) of the GPR50 gene. This alteration results from a C to T substitution at nucleotide position 55, causing the proline (P) at amino acid position 19 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
0.14
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
14
DANN
Uncertain
0.99
DEOGEN2
Benign
0.058
T
FATHMM_MKL
Benign
0.73
D
LIST_S2
Benign
0.68
T
M_CAP
Benign
0.042
D
MetaRNN
Benign
0.22
T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
0.90
L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.46
T
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.16
Sift
Uncertain
0.014
D
Sift4G
Uncertain
0.044
D
Polyphen
0.34
B
Vest4
0.33
MutPred
0.45
Gain of relative solvent accessibility (P = 0.09);
MVP
0.93
MPC
0.19
ClinPred
0.31
T
GERP RS
3.3
Varity_R
0.090
gMVP
0.33

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: rs2048681637; hg19: chrX-150345248; API