1-236142687-A-G

Position:

• chr1-236142687-A-G

Variant summary

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

The NM_003272.4(GPR137B):​c.65A>G​(p.Asp22Gly) 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. 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: 3.71

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08927539).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR137B	NM_003272.4	c.65A>G	p.Asp22Gly	missense_variant	1/7	ENST00000366592.8	NP_003263.1
GPR137B	XM_017002209.3	c.65A>G	p.Asp22Gly	missense_variant	1/7		XP_016857698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR137B	ENST00000366592.8	c.65A>G	p.Asp22Gly	missense_variant	1/7	1	NM_003272.4	ENSP00000355551.3
GPR137B	ENST00000366591.4	n.144A>G		non_coding_transcript_exon_variant	1/2	3
GPR137B	ENST00000419162.5	n.65A>G		non_coding_transcript_exon_variant	1/5	5		ENSP00000401841.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Jan 26, 2022

The c.65A>G (p.D22G) alteration is located in exon 1 (coding exon 1) of the GPR137B gene. This alteration results from a A to G substitution at nucleotide position 65, causing the aspartic acid (D) at amino acid position 22 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	Benign	0.12
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.81	T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.46	N
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.11
Sift	Benign	0.035	D
Sift4G	Benign	0.20	T
Polyphen		0.069	B
Vest4		0.15
MutPred		0.064		Gain of glycosylation at P23 (P = 0.123);
MVP		0.34
MPC		1.3
ClinPred		0.48	T
GERP RS		2.4
Varity_R		0.076
gMVP		0.47

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: chr1-236305987;