Genetic Variant GPR37L1:p.Thr217Met (chr1-202127760-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_004767.5(GPR37L1):c.650C>T(p.Thr217Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000887 in 1,578,548 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000091 ( 0 hom. )

Consequence

GPR37L1
NM_004767.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.09

Variant links:

Genes affected

GPR37L1 (HGNC:14923): (G protein-coupled receptor 37 like 1) Enables G protein-coupled peptide receptor activity; peptide binding activity; and prosaposin receptor activity. Involved in adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway and positive regulation of MAPK cascade. Located in plasma membrane. Part of receptor complex. [provided by Alliance of Genome Resources, Apr 2022]

GPR37L1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.41284955).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR37L1	NM_004767.5 link	c.650C>T	p.Thr217Met	missense_variant	Exon 2 of 2	ENST00000367282.6	NP_004758.3	O60883

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR37L1	ENST00000367282.6 link	c.650C>T	p.Thr217Met	missense_variant	Exon 2 of 2	1	NM_004767.5	ENSP00000356251.4		O60883

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152194

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000133

AC:

AN:

225632

Hom.:

AF XY:

0.00000829

AC XY:

AN XY:

120692

show subpopulations

Gnomad AFR exome

AF:

0.000125

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000973

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000911

AC:

AN:

1426354

Hom.:

Cov.:

AF XY:

0.00000851

AC XY:

AN XY:

704666

show subpopulations

Gnomad4 AFR exome

AF:

0.0000305

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000374

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000824

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.650C>T (p.T217M) alteration is located in exon 2 (coding exon 2) of the GPR37L1 gene. This alteration results from a C to T substitution at nucleotide position 650, causing the threonine (T) at amino acid position 217 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

0.21

BayesDel_addAF

Benign

-0.055

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.56

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.039

MetaRNN

Benign

0.41

MetaSVM

Benign

-0.86

PrimateAI

Uncertain

0.76

PROVEAN

Pathogenic

-4.5

REVEL

Benign

0.21

Sift

Uncertain

0.012

Sift4G

Pathogenic

0.0010

Polyphen

0.60

Vest4

0.48

MVP

0.79

MPC

0.28

ClinPred

0.90

GERP RS

3.2

Varity_R

0.17

gMVP

0.79

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