7-124746578-T-C

Position:

• chr7-124746578-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005302.5(GPR37):​c.1789A>G​(p.Ser597Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GPR37 NM_005302.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.75

Genes affected

GPR37 (HGNC:4494): (G protein-coupled receptor 37) This gene is a member of the G protein-coupled receptor family. The encoded protein contains seven transmembrane domains and is found in cell and endoplasmic reticulum membranes. G protein-coupled receptors are involved in translating outside signals into G protein mediated intracellular effects. This gene product interacts with Parkin and is involved in juvenile Parkinson disease. [provided by RefSeq, Oct 2012]

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=0.1749942).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR37	NM_005302.5	c.1789A>G	p.Ser597Gly	missense_variant	2/2	ENST00000303921.3	NP_005293.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR37	ENST00000303921.3	c.1789A>G	p.Ser597Gly	missense_variant	2/2	1	NM_005302.5	ENSP00000306449.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 11, 2024

The c.1789A>G (p.S597G) alteration is located in exon 2 (coding exon 2) of the GPR37 gene. This alteration results from a A to G substitution at nucleotide position 1789, causing the serine (S) at amino acid position 597 to be replaced by a glycine (G). 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	Pathogenic	0.68
BayesDel_addAF	Benign	0.0092	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.0081
Eigen_PC	Benign	0.15
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.0	L
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.19
Sift	Benign	0.20	T
Sift4G	Benign	0.56	T
Polyphen		0.010	B
Vest4		0.29
MutPred		0.25		Loss of glycosylation at S597 (P = 0.0091);
MVP		0.59
MPC		0.46
ClinPred		0.42	T
GERP RS		5.3
Varity_R		0.22
gMVP		0.45

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: chr7-124386632;