NM_001099652.2:c.52C>G

Variant names:

• chr14-52553199-C-G
• rs1445353398
• NM_001099652.2:c.52C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001099652.2(GPR137C):​c.52C>G​(p.Arg18Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000282 in 1,065,288 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign 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. R18S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: GPR137C NM_001099652.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34
• Publications: 0 publications found

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]

TXNDC16 (HGNC:19965): (thioredoxin domain containing 16) Located in endoplasmic reticulum lumen. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08412084).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099652.2. 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
	GPR137C	NM_001099652.2	MANE Select	c.52C>G	p.Arg18Gly	missense	Exon 1 of 7	NP_001093122.1	Q8N3F9
	GPR137C	NM_001353361.2		c.52C>G	p.Arg18Gly	missense	Exon 1 of 8	NP_001340290.1
	GPR137C	NR_148417.2		n.364C>G		non_coding_transcript_exon	Exon 1 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR137C	ENST00000321662.11	TSL:1 MANE Select	c.52C>G	p.Arg18Gly	missense	Exon 1 of 7	ENSP00000315106.6	Q8N3F9
	GPR137C	ENST00000866179.1		c.52C>G	p.Arg18Gly	missense	Exon 1 of 6	ENSP00000536238.1
	TXNDC16	ENST00000936707.1		c.-182+144G>C		intron	N/A	ENSP00000606766.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000282 AC: 3 AN: 1065288 Hom.: 0 Cov.: 29 AF XY: 0.00000397 AC XY: 2 AN XY: 503302

African (AFR) AF: 0.00 AC: 0 AN: 22168

American (AMR) AF: 0.00 AC: 0 AN: 7832

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13590

East Asian (EAS) AF: 0.00 AC: 0 AN: 24804

South Asian (SAS) AF: 0.00 AC: 0 AN: 19422

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20892

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2828

European-Non Finnish (NFE) AF: 0.00000329 AC: 3 AN: 911346

Other (OTH) AF: 0.00 AC: 0 AN: 42406

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	22
DANN	Benign	0.92
DEOGEN2	Benign	0.0046	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.48	T
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.3
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.080
Sift	Benign	0.057	T
Sift4G	Benign	0.18	T
Polyphen		0.0010	B
Vest4		0.15
MutPred		0.14		Gain of relative solvent accessibility (P = 0.0275)
MVP		0.082
MPC		1.8
ClinPred		0.14	T
GERP RS		2.9
PromoterAI		-0.029	Neutral
Varity_R		0.18
gMVP		0.54
Mutation Taster		=92/8	polymorphism

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

dbSNP: rs1445353398; hg19: chr14-53019917;