rs867948628

Variant names:

• chr14-52553272-C-A
• rs867948628
• NM_001099652.2:c.125C>A

Your query was ambiguous. Multiple possible variants found:

• chr14-52553272-C-A
• chr14-52553272-C-G
• chr14-52553272-C-T

Variant summary

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

The NM_001099652.2(GPR137C):​c.125C>A​(p.Pro42Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000534 in 1,311,870 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. P42L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000053 (0 hom.)
• Consequence: GPR137C NM_001099652.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.87
• 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 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.125C>A	p.Pro42Gln	missense	Exon 1 of 7	NP_001093122.1	Q8N3F9
	GPR137C	NM_001353361.2		c.125C>A	p.Pro42Gln	missense	Exon 1 of 8	NP_001340290.1
	GPR137C	NR_148417.2		n.437C>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.125C>A	p.Pro42Gln	missense	Exon 1 of 7	ENSP00000315106.6	Q8N3F9
	GPR137C	ENST00000866179.1		c.125C>A	p.Pro42Gln	missense	Exon 1 of 6	ENSP00000536238.1
	TXNDC16	ENST00000936707.1		c.-182+71G>T		intron	N/A	ENSP00000606766.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000534 AC: 7 AN: 1311870 Hom.: 0 Cov.: 34 AF XY: 0.00000312 AC XY: 2 AN XY: 640978

African (AFR) AF: 0.00 AC: 0 AN: 27976

American (AMR) AF: 0.00 AC: 0 AN: 29486

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22908

East Asian (EAS) AF: 0.00 AC: 0 AN: 29962

South Asian (SAS) AF: 0.00 AC: 0 AN: 70324

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34156

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3996

European-Non Finnish (NFE) AF: 0.00000674 AC: 7 AN: 1038484

Other (OTH) AF: 0.00 AC: 0 AN: 54578

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.22	T
Eigen	Benign	0.0015
Eigen_PC	Benign	0.011
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.68	T
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		1.9
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.061
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.74	P
Vest4		0.62
MutPred		0.37		Loss of loop (P = 0.0022)
MVP		0.068
MPC		1.4
ClinPred		0.86	D
GERP RS		2.5
PromoterAI		-0.012	Neutral
Varity_R		0.30
gMVP		0.55
Mutation Taster		=79/21	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: rs867948628; hg19: chr14-53019990;