Variant 1-236179908-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003272.4(GPR137B):c.717C>G(p.Ile239Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,446,452 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GPR137B
NM_003272.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.90

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23718807).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR137B	NM_003272.4 linkuse as main transcript	c.717C>G	p.Ile239Met	missense_variant	4/7	ENST00000366592.8	NP_003263.1	O60478
GPR137B	XM_017002209.3 linkuse as main transcript	c.717C>G	p.Ile239Met	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.717C>G	p.Ile239Met	missense_variant	4/7	1	NM_003272.4	ENSP00000355551.3		O60478

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000840

AC:

AN:

238058

Hom.:

AF XY:

0.00

AC XY:

AN XY:

128096

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000110

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1446452

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

718356

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 16, 2023

The c.717C>G (p.I239M) alteration is located in exon 4 (coding exon 4) of the GPR137B gene. This alteration results from a C to G substitution at nucleotide position 717, causing the isoleucine (I) at amino acid position 239 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

0.12

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.44

CADD

Benign

9.8

DANN

Uncertain

0.99

DEOGEN2

Benign

0.039

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.83

M_CAP

Benign

0.027

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.5

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.2

REVEL

Benign

0.26

Sift

Benign

0.18

Sift4G

Benign

0.23

Polyphen

0.95

Vest4

0.38

MutPred

0.26

Loss of sheet (P = 0.0817);

MVP

0.42

MPC

0.21

ClinPred

0.56

GERP RS

-3.7

Varity_R

0.074

gMVP

0.57

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