1-202123465-A-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/20 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

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]

LOC105371683 (HGNC:):

ACMG classification

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=0.1688436).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR37L1	NM_004767.5	c.502A>G	p.Ile168Val	missense_variant	Exon 1 of 2	ENST00000367282.6	NP_004758.3
LOC105371683	XR_922422.3	n.*122T>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR37L1	ENST00000367282.6	c.502A>G	p.Ile168Val	missense_variant	Exon 1 of 2	1	NM_004767.5	ENSP00000356251.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.502A>G (p.I168V) alteration is located in exon 1 (coding exon 1) of the GPR37L1 gene. This alteration results from a A to G substitution at nucleotide position 502, causing the isoleucine (I) at amino acid position 168 to be replaced by a valine (V). 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	0.13
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
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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-202092593;