Genetic Variant GPR137C:p.Pro42Leu (chr14-52553272-C-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.125C>T(p.Pro42Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000838 in 1,311,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000084 ( 0 hom. )

Consequence

GPR137C
NM_001099652.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.87

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=0.20230633).

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.125C>T	p.Pro42Leu	missense	Exon 1 of 7	NP_001093122.1	Q8N3F9
GPR137C	NM_001353361.2		c.125C>T	p.Pro42Leu	missense	Exon 1 of 8	NP_001340290.1
GPR137C	NR_148417.2		n.437C>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.125C>T	p.Pro42Leu	missense	Exon 1 of 7	ENSP00000315106.6	Q8N3F9
GPR137C	ENST00000866179.1		c.125C>T	p.Pro42Leu	missense	Exon 1 of 6	ENSP00000536238.1
TXNDC16	ENST00000936707.1		c.-182+71G>A		intron	N/A	ENSP00000606766.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000302

AC:

AN:

99244

AF XY:

0.0000183

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000543

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000248

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000838

AC:

AN:

1311870

Hom.:

Cov.:

AF XY:

0.00000468

AC XY:

AN XY:

640978

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27976

American (AMR)

AF:

0.0000339

AC:

AN:

29486

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22908

East Asian (EAS)

AF:

0.00

AC:

AN:

29962

South Asian (SAS)

AF:

0.0000569

AC:

AN:

70324

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34156

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3996

European-Non Finnish (NFE)

AF:

0.00000481

AC:

AN:

1038484

Other (OTH)

AF:

0.0000183

AC:

AN:

54578

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.74

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.20

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PhyloP100

1.9

PrimateAI

Pathogenic

0.92

PROVEAN

Pathogenic

-4.9

REVEL

Benign

0.16

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.054

Polyphen

0.47

Vest4

0.25

MutPred

0.41

Gain of helix (P = 0.0022)

MVP

0.11

MPC

1.5

ClinPred

0.29

GERP RS

2.5

PromoterAI

-0.0012

Neutral

(source)

Varity_R

0.20

gMVP

0.59

Mutation Taster

=80/20

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over