chrX-151180098-A-G
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_004224.3(GPR50):āc.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
NM_004224.3 missense
Scores
5
10
2
Clinical Significance
Conservation
PhyloP100: 7.39
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]
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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 |
---|---|---|---|---|---|---|---|
GPR50 | NM_004224.3 | c.515A>G | p.Asp172Gly | missense_variant | 2/2 | ENST00000218316.4 | |
GPR50 | XM_011531216.3 | c.1+6A>G | splice_donor_region_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GPR50 | ENST00000218316.4 | c.515A>G | p.Asp172Gly | missense_variant | 2/2 | 1 | NM_004224.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000180 AC: 2AN: 110891Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 33175
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GnomAD3 exomes AF: 0.00000553 AC: 1AN: 180922Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 66728
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GnomAD4 exome AF: 0.0000128 AC: 14AN: 1096638Hom.: 0 Cov.: 33 AF XY: 0.0000138 AC XY: 5AN XY: 362120
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GnomAD4 genome AF: 0.0000180 AC: 2AN: 110891Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 33175
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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 submitter | clinical testing | Ambry Genetics | May 17, 2023 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
B
Vest4
MutPred
Loss of stability (P = 0.178);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at