14-52553547-C-G

Variant names:

• chr14-52553547-C-G
• rs1193922795
• NM_001099652.2:c.400C>G

Variant summary

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

The NM_001099652.2(GPR137C):​c.400C>G​(p.Leu134Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,607,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. L134F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: GPR137C NM_001099652.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.03

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.913

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR137C	NM_001099652.2	c.400C>G	p.Leu134Val	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.400C>G	p.Leu134Val	missense_variant	Exon 1 of 7	1	NM_001099652.2	ENSP00000315106.6
GPR137C	ENST00000542169.6	c.259C>G	p.Leu87Val	missense_variant	Exon 1 of 8	1		ENSP00000439165.2
GPR137C	ENST00000555622.1	c.127C>G	p.Leu43Val	missense_variant	Exon 1 of 5	3		ENSP00000452563.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152164 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455670 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 724232

Gnomad4 AFR exome AF: 0.0000299

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152164 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74346

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.97	D
M_CAP	Pathogenic	0.54	D
MetaRNN	Pathogenic	0.91	D
MetaSVM	Benign	-0.76	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.5	N
REVEL	Uncertain	0.39
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.89	P
Vest4		0.86
MutPred		0.77		Gain of sheet (P = 0.1208);
MVP		0.23
MPC		0.72
ClinPred		0.98	D
GERP RS		3.9
Varity_R		0.62
gMVP		0.48

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: rs1193922795; hg19: chr14-53020265;