Genetic Variant NM_004224.3:c.92T>C (chrX-151176813-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_004224.3(GPR50):c.92T>C(p.Met31Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000291 in 1,201,521 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000054 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.000027 ( 0 hom. 7 hem. )

Consequence

GPR50
NM_004224.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.39

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:

GPR50-AS1 (HGNC:40259): (GPR50 antisense RNA 1)

GPR50-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 7 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.92T>C	p.Met31Thr	missense	Exon 1 of 2	NP_004215.2	Q13585
	GPR50-AS1	NR_135300.1		n.523A>G		non_coding_transcript_exon	Exon 2 of 3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPR50	ENST00000218316.4	TSL:1 MANE Select	c.92T>C	p.Met31Thr	missense	Exon 1 of 2	ENSP00000218316.3	Q13585
GPR50-AS1	ENST00000454196.1	TSL:2	n.523A>G		non_coding_transcript_exon	Exon 2 of 3
GPR50-AS1	ENST00000835195.1		n.492A>G		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes

AF:

0.0000540

AC:

AN:

111168

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:

0.000113

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000111

AC:

AN:

180456

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:

0.0000247

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000266

AC:

AN:

1090353

Hom.:

Cov.:

AF XY:

0.0000197

AC XY:

AN XY:

355997

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26239

American (AMR)

AF:

0.00

AC:

AN:

35167

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19320

East Asian (EAS)

AF:

0.00

AC:

AN:

30154

South Asian (SAS)

AF:

0.00

AC:

AN:

53919

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40532

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4096

European-Non Finnish (NFE)

AF:

0.0000347

AC:

AN:

835088

Other (OTH)

AF:

0.00

AC:

AN:

45838

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.0000540

AC:

AN:

111168

Hom.:

Cov.:

AF XY:

0.0000300

AC XY:

AN XY:

33382

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30497

American (AMR)

AF:

0.00

AC:

AN:

10587

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2640

East Asian (EAS)

AF:

0.00

AC:

AN:

3496

South Asian (SAS)

AF:

0.00

AC:

AN:

2547

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6023

Middle Eastern (MID)

AF:

0.00

AC:

AN:

235

European-Non Finnish (NFE)

AF:

0.000113

AC:

AN:

52978

Other (OTH)

AF:

0.00

AC:

AN:

1486

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000302

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000156

AC:

ExAC

AF:

0.00000828

AC:

EpiCase

AF:

0.0000547

EpiControl

AF:

0.0000598

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

0.25

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.086

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.61

M_CAP

Benign

0.012

MetaRNN

Uncertain

0.58

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

PhyloP100

3.4

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.8

REVEL

Benign

0.16

Sift

Uncertain

0.027

Sift4G

Benign

0.067

Polyphen

0.061

Vest4

0.63

MVP

0.85

MPC

0.17

ClinPred

0.25

GERP RS

4.2

PromoterAI

0.032

Neutral

(source)

Varity_R

0.37

gMVP

0.75

Mutation Taster

=77/23

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