Genetic Variant GPR50:p.Val157Phe (chrX-151180052-G-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_004224.3(GPR50):c.469G>T(p.Val157Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000711 in 1,209,382 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 22 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.000077 ( 0 hom. 22 hem. )

Consequence

GPR50
NM_004224.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.30

Publications

2 publications found

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 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1397816).

BS2

High Hemizygotes in GnomAdExome4 at 22 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004224.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR50	NM_004224.3	MANE Select	c.469G>T	p.Val157Phe	missense	Exon 2 of 2	NP_004215.2	Q13585

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR50	ENST00000218316.4	TSL:1 MANE Select	c.469G>T	p.Val157Phe	missense	Exon 2 of 2	ENSP00000218316.3	Q13585

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111715

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000376

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000550

AC:

AN:

181821

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000765

AC:

AN:

1097667

Hom.:

Cov.:

AF XY:

0.0000606

AC XY:

AN XY:

363031

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26393

American (AMR)

AF:

0.00

AC:

AN:

35206

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19383

East Asian (EAS)

AF:

0.00

AC:

AN:

30202

South Asian (SAS)

AF:

0.00

AC:

AN:

54124

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40439

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4135

European-Non Finnish (NFE)

AF:

0.0000950

AC:

AN:

841714

Other (OTH)

AF:

0.0000868

AC:

AN:

46071

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000179

AC:

AN:

111715

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33907

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30628

American (AMR)

AF:

0.00

AC:

AN:

10603

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2647

East Asian (EAS)

AF:

0.00

AC:

AN:

3571

South Asian (SAS)

AF:

0.00

AC:

AN:

2630

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6065

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.0000376

AC:

AN:

53145

Other (OTH)

AF:

0.00

AC:

AN:

1507

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.0040

(source)

DANN

Benign

0.90

DEOGEN2

Uncertain

0.47

FATHMM_MKL

Benign

0.068

LIST_S2

Benign

0.31

M_CAP

Benign

0.0075

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.21

PhyloP100

-1.3

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.047

Sift

Benign

0.096

Sift4G

Benign

0.12

Polyphen

0.0030

Vest4

0.19

MutPred

0.61

Loss of stability (P = 0.1052)

MVP

0.56

MPC

0.20

ClinPred

0.063

GERP RS

-7.5

Varity_R

0.25

gMVP

0.73

Mutation Taster

=92/8

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over