GPR37L1 p.Arg21Ser

Variant names:

• chr1-202123026-G-T
• NM_004767.5:c.63G>T
• GPR37L1 p.Arg21Ser

Your query was ambiguous. Multiple possible variants found:

• chr1-202123026-G-T
• chr1-202123026-G-C
• chr1-202123024-AG-TC
• chr1-202123024-AGG-TCT
• chr1-202123024-AGG-TCC
• chr1-202123024-AGG-TCA

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.63G>T​(p.Arg21Ser) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: GPR37L1 NM_004767.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.114
• 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=0.08147836).

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.63G>T	p.Arg21Ser	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.63G>T	p.Arg21Ser	missense	Exon 1 of 2	ENSP00000356251.4	O60883
	GPR37L1	ENST00000683302.1		c.63G>T	p.Arg21Ser	missense	Exon 1 of 3	ENSP00000507885.1	A0A804HKD8
	GPR37L1	ENST00000683557.1		c.63G>T	p.Arg21Ser	missense	Exon 1 of 3	ENSP00000508029.1	A0A804HKQ6

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 49

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	2.8
DANN	Benign	0.84
DEOGEN2	Benign	0.043	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.057	D
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-0.93	T
PhyloP100		0.11
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.18
Sift	Benign	0.082	T
Sift4G	Benign	0.15	T
PromoterAI		-0.046	Neutral
Varity_R		0.11
gMVP		0.48
Mutation Taster		=90/10	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-202092154;