chrX-151176889-C-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_004224.3(GPR50):ā€‹c.168C>Gā€‹(p.Asn56Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000367 in 1,090,133 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 23)
Exomes š‘“: 0.0000037 ( 0 hom. 2 hem. )

Consequence

GPR50
NM_004224.3 missense

Scores

2
8
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.02
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 -4 ACMG points.

BS2
High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GPR50NM_004224.3 linkuse as main transcriptc.168C>G p.Asn56Lys missense_variant 1/2 ENST00000218316.4
GPR50-AS1NR_135300.1 linkuse as main transcriptn.461-14G>C splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GPR50ENST00000218316.4 linkuse as main transcriptc.168C>G p.Asn56Lys missense_variant 1/21 NM_004224.3 P1
GPR50-AS1ENST00000454196.1 linkuse as main transcriptn.461-14G>C splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
AF:
0.00000367
AC:
4
AN:
1090133
Hom.:
0
Cov.:
28
AF XY:
0.00000562
AC XY:
2
AN XY:
355973
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:
0.00000478
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
23

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 21, 2023The c.168C>G (p.N56K) 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 168, causing the asparagine (N) at amino acid position 56 to be replaced by a lysine (K). 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
0.86
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
20
DANN
Benign
0.96
DEOGEN2
Uncertain
0.53
D
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.93
D
M_CAP
Benign
0.084
D
MetaRNN
Uncertain
0.61
D
MetaSVM
Benign
-0.49
T
MutationAssessor
Uncertain
2.8
M
MutationTaster
Benign
0.91
N
PrimateAI
Uncertain
0.50
T
PROVEAN
Pathogenic
-4.5
D
REVEL
Benign
0.25
Sift
Uncertain
0.021
D
Sift4G
Uncertain
0.016
D
Polyphen
0.20
B
Vest4
0.51
MutPred
0.72
Gain of methylation at N56 (P = 0.0194);
MVP
0.97
MPC
0.22
ClinPred
0.82
D
GERP RS
3.5
Varity_R
0.33
gMVP
0.40

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: rs1246151000; hg19: chrX-150345361; API