chr14-52553587-C-A

Variant names:

• chr14-52553587-C-A
• rs777750722
• NM_001099652.2:c.440C>A

Variant summary

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

The NM_001099652.2(GPR137C):​c.440C>A​(p.Ala147Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000151 in 1,393,036 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. A147V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: GPR137C NM_001099652.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.92

Genes affected

GPR137C (HGNC:25445): (G protein-coupled receptor 137C) Predicted to be involved in positive regulation of TORC1 signaling. Located in lysosomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

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
GPR137C	NM_001099652.2	c.440C>A	p.Ala147Glu	missense_variant	Exon 1 of 7	ENST00000321662.11	NP_001093122.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR137C	ENST00000321662.11	c.440C>A	p.Ala147Glu	missense_variant	Exon 1 of 7	1	NM_001099652.2	ENSP00000315106.6
GPR137C	ENST00000542169.6	c.299C>A	p.Ala100Glu	missense_variant	Exon 1 of 8	1		ENSP00000439165.2
GPR137C	ENST00000555622.1	c.167C>A	p.Ala56Glu	missense_variant	Exon 1 of 5	3		ENSP00000452563.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000151 AC: 21 AN: 1393036 Hom.: 0 Cov.: 34 AF XY: 0.0000102 AC XY: 7 AN XY: 689256

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.0000186

Gnomad4 OTH exome AF: 0.0000174

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Benign	0.097
Eigen_PC	Benign	0.031
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.22
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.98	D
Vest4		0.73
MutPred		0.48		Gain of relative solvent accessibility (P = 0.09);
MVP		0.068
MPC		0.60
ClinPred		0.97	D
GERP RS		3.7
Varity_R		0.44
gMVP		0.84

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: rs777750722; hg19: chr14-53020305;