Genetic Variant GPR137C:p.Val3Leu (chr14-52553154-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001099652.2(GPR137C):c.7G>T(p.Val3Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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. V3M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GPR137C
NM_001099652.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.29

Publications

0 publications found

Variant links:

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]

GPR137C links:

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

TXNDC16 links:

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ACMG classification

Classification was made for transcript

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=0.087222695).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPR137C	NM_001099652.2	MANE Select	c.7G>T	p.Val3Leu	missense	Exon 1 of 7	NP_001093122.1	Q8N3F9
GPR137C	NM_001353361.2		c.7G>T	p.Val3Leu	missense	Exon 1 of 8	NP_001340290.1
GPR137C	NR_148417.2		n.319G>T		non_coding_transcript_exon	Exon 1 of 8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPR137C	ENST00000321662.11	TSL:1 MANE Select	c.7G>T	p.Val3Leu	missense	Exon 1 of 7	ENSP00000315106.6	Q8N3F9
GPR137C	ENST00000866179.1		c.7G>T	p.Val3Leu	missense	Exon 1 of 6	ENSP00000536238.1
TXNDC16	ENST00000936707.1		c.-182+189C>A		intron	N/A	ENSP00000606766.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1020114

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

481100

African (AFR)

AF:

0.00

AC:

AN:

20376

American (AMR)

AF:

0.00

AC:

AN:

6476

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11756

East Asian (EAS)

AF:

0.00

AC:

AN:

18268

South Asian (SAS)

AF:

0.00

AC:

AN:

18968

European-Finnish (FIN)

AF:

0.00

AC:

AN:

18370

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2602

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

884074

Other (OTH)

AF:

0.00

AC:

AN:

39224

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0019

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.16

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.50

M_CAP

Benign

0.070

MetaRNN

Benign

0.087

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

3.3

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.29

REVEL

Benign

0.090

Sift

Benign

0.31

Sift4G

Benign

0.45

Polyphen

0.0

Vest4

0.28

MutPred

0.16

Loss of sheet (P = 0.0181)

MVP

0.068

MPC

1.4

ClinPred

0.46

GERP RS

4.1

PromoterAI

0.025

Neutral

(source)

Varity_R

0.10

gMVP

0.34

Mutation Taster

=92/8

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over