chr1-236179964-T-C

Position:

• chr1-236179964-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_003272.4(GPR137B):​c.773T>C​(p.Leu258Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: GPR137B NM_003272.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57

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]

GPR137B (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.908

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR137B	NM_003272.4	c.773T>C	p.Leu258Pro	missense_variant	4/7	ENST00000366592.8	NP_003263.1
GPR137B	XM_017002209.3	c.773T>C	p.Leu258Pro	missense_variant	4/7		XP_016857698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR137B	ENST00000366592.8	c.773T>C	p.Leu258Pro	missense_variant	4/7	1	NM_003272.4	ENSP00000355551.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

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 10, 2024

The c.773T>C (p.L258P) alteration is located in exon 4 (coding exon 4) of the GPR137B gene. This alteration results from a T to C substitution at nucleotide position 773, causing the leucine (L) at amino acid position 258 to be replaced by a proline (P). 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	0.91
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.80	T
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.91	D
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Pathogenic	0.71
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		1.0
MutPred		0.68		Loss of stability (P = 0.0062);
MVP		0.78
MPC		0.86
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.88
gMVP		0.95

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: chr1-236343264;