14-52553587-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. A147G) 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
• Publications: 1 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.440C>A	p.Ala147Glu	missense	Exon 1 of 7	NP_001093122.1	Q8N3F9
	GPR137C	NM_001353361.2		c.440C>A	p.Ala147Glu	missense	Exon 1 of 8	NP_001340290.1
	GPR137C	NR_148417.2		n.752C>A		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.440C>A	p.Ala147Glu	missense	Exon 1 of 7	ENSP00000315106.6	Q8N3F9
	GPR137C	ENST00000542169.6	TSL:1	c.299C>A	p.Ala100Glu	missense	Exon 1 of 8	ENSP00000439165.2	H0YFL6
	GPR137C	ENST00000866179.1		c.440C>A	p.Ala147Glu	missense	Exon 1 of 6	ENSP00000536238.1

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

African (AFR) AF: 0.00 AC: 0 AN: 31290

American (AMR) AF: 0.00 AC: 0 AN: 40124

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24808

East Asian (EAS) AF: 0.00 AC: 0 AN: 35162

South Asian (SAS) AF: 0.00 AC: 0 AN: 78896

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5608

European-Non Finnish (NFE) AF: 0.0000186 AC: 20 AN: 1073260

Other (OTH) AF: 0.0000174 AC: 1 AN: 57354

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		4.9
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
PromoterAI		0.019	Neutral
Varity_R		0.44
gMVP		0.84
Mutation Taster		=62/38	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: rs777750722; hg19: chr14-53020305;