chr1-236143013-C-G

Variant names:

• chr1-236143013-C-G
• NM_003272.4:c.391C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_003272.4(GPR137B):​c.391C>G​(p.Leu131Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPR137B NM_003272.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.90
• Publications: 0 publications found

Genes affected

GPR137B (HGNC:11862): (G protein-coupled receptor 137B) Involved in several processes, including positive regulation of TORC1 signaling; positive regulation of protein localization to lysosome; and regulation of GTPase activity. Located in lysosomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.807

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003272.4. 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
	GPR137B	NM_003272.4	MANE Select	c.391C>G	p.Leu131Val	missense	Exon 1 of 7	NP_003263.1	O60478

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR137B	ENST00000366592.8	TSL:1 MANE Select	c.391C>G	p.Leu131Val	missense	Exon 1 of 7	ENSP00000355551.3	O60478
	GPR137B	ENST00000889786.1		c.391C>G	p.Leu131Val	missense	Exon 1 of 8	ENSP00000559845.1
	GPR137B	ENST00000889783.1		c.391C>G	p.Leu131Val	missense	Exon 1 of 8	ENSP00000559842.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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	Uncertain	0.43
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.024	T
MetaRNN	Pathogenic	0.81	D
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		5.9
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.30
Sift	Benign	0.033	D
Sift4G	Uncertain	0.016	D
Polyphen		0.91	P
Vest4		0.91
MutPred		0.61		Gain of catalytic residue at L131 (P = 0.0859)
MVP		0.41
MPC		1.5
ClinPred		0.97	D
GERP RS		3.8
PromoterAI		0.011	Neutral
Varity_R		0.53
gMVP		0.66
Mutation Taster		=50/50

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: chr1-236306313;