Variant 1-236179888-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003272.4(GPR137B):c.697G>A(p.Val233Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 1,584,088 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00011 ( 1 hom. )

Consequence

GPR137B
NM_003272.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.66

Variant links:

Genes affected

GPR137B (HGNC:11862): (G protein-coupled receptor 137B) Involved in several processes, including positive regulation of TORC1 signaling; positive regulation of protein localization to lysosome; and regulation of GTPase activity. Located in lysosomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

GPR137B links:

GPR137B (HGNC:):

GPR137B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR137B	NM_003272.4 linkuse as main transcript	c.697G>A	p.Val233Met	missense_variant	4/7	ENST00000366592.8	NP_003263.1	O60478
GPR137B	XM_017002209.3 linkuse as main transcript	c.697G>A	p.Val233Met	missense_variant	4/7		XP_016857698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR137B	ENST00000366592.8 linkuse as main transcript	c.697G>A	p.Val233Met	missense_variant	4/7	1	NM_003272.4	ENSP00000355551.3		O60478

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.0000706

AC:

AN:

226520

Hom.:

AF XY:

0.0000744

AC XY:

AN XY:

120952

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000950

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000166

Gnomad FIN exome

AF:

0.0000500

Gnomad NFE exome

AF:

0.0000772

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000105

AC:

151

AN:

1431830

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

709052

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000721

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000752

Gnomad4 FIN exome

AF:

0.0000575

Gnomad4 NFE exome

AF:

0.0000720

Gnomad4 OTH exome

AF:

0.000118

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.0000392

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.0000412

AC:

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

Sep 01, 2021

The c.697G>A (p.V233M) alteration is located in exon 4 (coding exon 4) of the GPR137B gene. This alteration results from a G to A substitution at nucleotide position 697, causing the valine (V) at amino acid position 233 to be replaced by a methionine (M). 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

Benign

0.16

BayesDel_addAF

Uncertain

0.057

BayesDel_noAF

Uncertain

0.11

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.024

MetaRNN

Uncertain

0.73

MetaSVM

Benign

-0.44

MutationAssessor

Uncertain

2.4

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.8

REVEL

Benign

0.28

Sift

Benign

0.076

Sift4G

Benign

0.14

Polyphen

1.0

Vest4

0.87

MVP

0.55

MPC

0.36

ClinPred

0.17

GERP RS

5.5

Varity_R

0.21

gMVP

0.53

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over