Genetic Variant GPR137C:p.Ala48Ser (chr14-52553289-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.142G>T(p.Ala48Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000138 in 1,520,714 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: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

GPR137C
NM_001099652.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.13

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=0.11637184).

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.142G>T	p.Ala48Ser	missense	Exon 1 of 7	NP_001093122.1	Q8N3F9
GPR137C	NM_001353361.2		c.142G>T	p.Ala48Ser	missense	Exon 1 of 8	NP_001340290.1
GPR137C	NR_148417.2		n.454G>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.142G>T	p.Ala48Ser	missense	Exon 1 of 7	ENSP00000315106.6	Q8N3F9
GPR137C	ENST00000542169.6	TSL:1	c.1G>T	p.Ala1Ser	missense	Exon 1 of 8	ENSP00000439165.2	H0YFL6
GPR137C	ENST00000866179.1		c.142G>T	p.Ala48Ser	missense	Exon 1 of 6	ENSP00000536238.1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

151970

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000139

AC:

AN:

143788

AF XY:

0.0000127

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000160

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000132

AC:

AN:

1368744

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

673610

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30768

American (AMR)

AF:

0.00

AC:

AN:

34354

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24548

East Asian (EAS)

AF:

0.00

AC:

AN:

34564

South Asian (SAS)

AF:

0.0000262

AC:

AN:

76266

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36502

Middle Eastern (MID)

AF:

0.000225

AC:

AN:

4438

European-Non Finnish (NFE)

AF:

0.0000140

AC:

AN:

1070272

Other (OTH)

AF:

0.00

AC:

AN:

57032

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

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

AF:

0.0000197

AC:

AN:

151970

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74222

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41440

American (AMR)

AF:

0.00

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10530

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67960

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000724

Hom.:

Bravo

AF:

0.0000189

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

Benign

0.11

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.011

Eigen

Benign

-0.0029

Eigen_PC

Benign

0.081

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.65

M_CAP

Benign

0.074

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.87

MutationAssessor

Benign

-0.12

PhyloP100

5.1

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.20

REVEL

Benign

0.080

Sift

Benign

0.14

Sift4G

Benign

0.26

Polyphen

0.0020

Vest4

0.31

MutPred

0.37

Loss of helix (P = 0.0041)

MVP

0.043

MPC

1.3

ClinPred

0.14

GERP RS

4.4

PromoterAI

0.026

Neutral

(source)

Varity_R

0.12

gMVP

0.26

Mutation Taster

=83/17

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

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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