NM_004767.5:c.502A>G

Variant names:

• chr1-202123465-A-G
• NM_004767.5:c.502A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004767.5(GPR37L1):​c.502A>G​(p.Ile168Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: GPR37L1 NM_004767.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.20
• Publications: 0 publications found

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]

ENSG00000294430 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1688436).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004767.5. 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
	GPR37L1	NM_004767.5	MANE Select	c.502A>G	p.Ile168Val	missense	Exon 1 of 2	NP_004758.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR37L1	ENST00000367282.6	TSL:1 MANE Select	c.502A>G	p.Ile168Val	missense	Exon 1 of 2	ENSP00000356251.4	O60883
	GPR37L1	ENST00000683302.1		c.502A>G	p.Ile168Val	missense	Exon 1 of 3	ENSP00000507885.1	A0A804HKD8
	GPR37L1	ENST00000683557.1		c.502A>G	p.Ile168Val	missense	Exon 1 of 3	ENSP00000508029.1	A0A804HKQ6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.22
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.89	T
PhyloP100		3.2
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.090
Sift	Benign	0.12	T
Sift4G	Benign	0.37	T
Polyphen		0.0050	B
Vest4		0.22
MutPred		0.55		Loss of glycosylation at S167 (P = 0.1249)
MVP		0.66
MPC		0.16
ClinPred		0.39	T
GERP RS		3.9
Varity_R		0.076
gMVP		0.23
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

hg19: chr1-202092593;