1-202127996-G-A

Variant summary

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

The ENST00000367282.6(GPR37L1):​c.886G>A​(p.Glu296Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 1,613,946 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

GPR37L1
ENST00000367282.6 missense

Scores

2
10
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91
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]

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
GPR37L1NM_004767.5 linkuse as main transcriptc.886G>A p.Glu296Lys missense_variant 2/2 ENST00000367282.6 NP_004758.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GPR37L1ENST00000367282.6 linkuse as main transcriptc.886G>A p.Glu296Lys missense_variant 2/21 NM_004767.5 ENSP00000356251 P1

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152092
Hom.:
0
Cov.:
32
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:
0.000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000108
AC:
27
AN:
250648
Hom.:
0
AF XY:
0.000111
AC XY:
15
AN XY:
135460
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.000139
Gnomad NFE exome
AF:
0.000177
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000109
AC:
160
AN:
1461854
Hom.:
0
Cov.:
34
AF XY:
0.000103
AC XY:
75
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.000131
Gnomad4 NFE exome
AF:
0.000129
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
AF:
0.0000657
AC:
10
AN:
152092
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74294
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:
0.000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000141
Hom.:
0
Bravo
AF:
0.0000416
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000778
AC:
3
ExAC
AF:
0.000148
AC:
18
EpiCase
AF:
0.000109
EpiControl
AF:
0.000119

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 submitterclinical testingAmbry GeneticsSep 07, 2022The c.886G>A (p.E296K) alteration is located in exon 2 (coding exon 2) of the GPR37L1 gene. This alteration results from a G to A substitution at nucleotide position 886, causing the glutamic acid (E) at amino acid position 296 to be replaced by a lysine (K). 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
0.33
BayesDel_addAF
Benign
-0.081
T
BayesDel_noAF
Benign
-0.090
CADD
Pathogenic
29
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.19
T
Eigen
Uncertain
0.48
Eigen_PC
Uncertain
0.52
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.94
D
M_CAP
Pathogenic
0.32
D
MetaRNN
Uncertain
0.46
T
MetaSVM
Benign
-0.31
T
MutationTaster
Benign
0.98
D
PrimateAI
Uncertain
0.52
T
PROVEAN
Uncertain
-2.5
D
REVEL
Uncertain
0.52
Sift
Uncertain
0.0050
D
Sift4G
Uncertain
0.013
D
Polyphen
0.97
D
Vest4
0.28
MVP
0.91
MPC
0.61
ClinPred
0.43
T
GERP RS
5.0
Varity_R
0.32
gMVP
0.60

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.

Other links and lift over

dbSNP: rs767987863; hg19: chr1-202097124; COSMIC: COSV66162563; API