X-151176866-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_004224.3(GPR50):​c.145G>T​(p.Val49Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Consequence

GPR50
NM_004224.3 missense

Scores

9
6
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.58
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)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.925

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GPR50NM_004224.3 linkuse as main transcriptc.145G>T p.Val49Phe missense_variant 1/2 ENST00000218316.4
GPR50-AS1NR_135300.1 linkuse as main transcriptn.470C>A 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.145G>T p.Val49Phe missense_variant 1/21 NM_004224.3 P1
GPR50-AS1ENST00000454196.1 linkuse as main transcriptn.470C>A non_coding_transcript_exon_variant 2/32

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD4 exome
Cov.:
28
GnomAD4 genome
Cov.:
22
Bravo
AF:
0.00000378

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 GeneticsMar 18, 2024The c.145G>T (p.V49F) alteration is located in exon 1 (coding exon 1) of the GPR50 gene. This alteration results from a G to T substitution at nucleotide position 145, causing the valine (V) at amino acid position 49 to be replaced by a phenylalanine (F). 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
Pathogenic
0.55
D
BayesDel_noAF
Pathogenic
0.55
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.57
D
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.83
T
M_CAP
Uncertain
0.23
D
MetaRNN
Pathogenic
0.92
D
MetaSVM
Pathogenic
0.81
D
MutationAssessor
Pathogenic
4.2
H
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.69
T
PROVEAN
Uncertain
-3.6
D
REVEL
Pathogenic
0.86
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0010
D
Polyphen
1.0
D
Vest4
0.83
MutPred
0.72
Gain of MoRF binding (P = 0.1577);
MVP
0.96
MPC
0.73
ClinPred
1.0
D
GERP RS
4.4
Varity_R
0.91
gMVP
0.97

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: rs1431717214; hg19: chrX-150345338; API