1-202123453-G-T

Variant names:

• chr1-202123453-G-T
• rs776830420
• NM_004767.5:c.490G>T

Variant summary

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

The NM_004767.5(GPR37L1):​c.490G>T​(p.Ala164Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000889 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A164T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: GPR37L1 NM_004767.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.59

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR37L1	NM_004767.5	c.490G>T	p.Ala164Ser	missense_variant	Exon 1 of 2	ENST00000367282.6	NP_004758.3
LOC105371683	XR_922422.3	n.*134C>A		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR37L1	ENST00000367282.6	c.490G>T	p.Ala164Ser	missense_variant	Exon 1 of 2	1	NM_004767.5	ENSP00000356251.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251200 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135762

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000889 AC: 13 AN: 1461858 Hom.: 0 Cov.: 34 AF XY: 0.00000963 AC XY: 7 AN XY: 727230

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000108

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.43
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.90	T
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.21
Sift	Benign	0.15	T
Sift4G	Benign	0.074	T
Polyphen		0.78	P
Vest4		0.51
MutPred		0.54		Gain of ubiquitination at K162 (P = 0.0856);
MVP		0.71
MPC		0.63
ClinPred		0.96	D
GERP RS		5.0
Varity_R		0.15
gMVP		0.44

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

Other links and lift over

dbSNP: rs776830420; hg19: chr1-202092581;