dbSNP rs755414121: GPR50:p.Asp172Gly (chrX-151180098-A-G) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP3BS2

The NM_004224.3(GPR50):c.515A>G(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 (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000013 ( 0 hom. 5 hem. )

Consequence

GPR50
NM_004224.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.39

Publications

0 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 -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.811

BS2

High Hemizygotes in GnomAdExome4 at 5 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.515A>G	p.Asp172Gly	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.515A>G	p.Asp172Gly	missense	Exon 2 of 2	ENSP00000218316.3	Q13585

Frequencies

GnomAD3 genomes

AF:

0.0000180

AC:

AN:

110891

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:

0.0000378

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000553

AC:

AN:

180922

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:

0.0000128

AC:

AN:

1096638

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

362120

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26385

American (AMR)

AF:

0.00

AC:

AN:

35206

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19381

East Asian (EAS)

AF:

0.00

AC:

AN:

30202

South Asian (SAS)

AF:

0.00

AC:

AN:

54120

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39757

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4130

European-Non Finnish (NFE)

AF:

0.0000155

AC:

AN:

841385

Other (OTH)

AF:

0.0000217

AC:

AN:

46072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

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:

0.0000180

AC:

AN:

110891

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33175

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30333

American (AMR)

AF:

0.00

AC:

AN:

10517

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2638

East Asian (EAS)

AF:

0.00

AC:

AN:

3541

South Asian (SAS)

AF:

0.00

AC:

AN:

2580

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5957

Middle Eastern (MID)

AF:

0.00

AC:

AN:

235

European-Non Finnish (NFE)

AF:

0.0000378

AC:

AN:

52921

Other (OTH)

AF:

0.00

AC:

AN:

1491

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.750

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000346

AC:

ClinVar

ClinVar submissions as Germline

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

Pathogenic

0.95

BayesDel_addAF

Uncertain

0.071

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.58

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.92

M_CAP

Uncertain

0.16

MetaRNN

Pathogenic

0.81

MetaSVM

Uncertain

0.30

MutationAssessor

Pathogenic

3.0

PhyloP100

7.4

PrimateAI

Uncertain

0.55

PROVEAN

Pathogenic

-6.8

REVEL

Uncertain

0.54

Sift

Uncertain

0.011

Sift4G

Uncertain

0.010

Polyphen

0.21

Vest4

0.64

MutPred

0.60

Loss of stability (P = 0.178)

MVP

0.95

MPC

0.48

ClinPred

0.96

GERP RS

4.3

Varity_R

0.78

gMVP

0.87

Mutation Taster

=60/40

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over