Genetic Variant GPR137C:p.Ala9Val (chr14-52553173-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001099652.2(GPR137C):c.26C>T(p.Ala9Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000268 in 1,179,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000093 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00029 ( 0 hom. )

Consequence

GPR137C
NM_001099652.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.758

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07390535).

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.26C>T	p.Ala9Val	missense	Exon 1 of 7	NP_001093122.1	Q8N3F9
GPR137C	NM_001353361.2		c.26C>T	p.Ala9Val	missense	Exon 1 of 8	NP_001340290.1
GPR137C	NR_148417.2		n.338C>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.26C>T	p.Ala9Val	missense	Exon 1 of 7	ENSP00000315106.6	Q8N3F9
GPR137C	ENST00000866179.1		c.26C>T	p.Ala9Val	missense	Exon 1 of 6	ENSP00000536238.1
TXNDC16	ENST00000936707.1		c.-182+170G>A		intron	N/A	ENSP00000606766.1

Frequencies

GnomAD3 genomes

AF:

0.0000927

AC:

AN:

151102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000207

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000294

AC:

302

AN:

1028860

Hom.:

Cov.:

AF XY:

0.000280

AC XY:

136

AN XY:

485250

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20702

American (AMR)

AF:

0.00

AC:

AN:

6766

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12058

East Asian (EAS)

AF:

0.00

AC:

AN:

19556

South Asian (SAS)

AF:

0.00

AC:

AN:

19062

European-Finnish (FIN)

AF:

0.00

AC:

AN:

18986

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2642

European-Non Finnish (NFE)

AF:

0.000325

AC:

289

AN:

889262

Other (OTH)

AF:

0.000326

AC:

AN:

39826

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.0000927

AC:

AN:

151102

Hom.:

Cov.:

AF XY:

0.0000407

AC XY:

AN XY:

73764

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41302

American (AMR)

AF:

0.00

AC:

AN:

15160

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

5138

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10248

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000207

AC:

AN:

67668

Other (OTH)

AF:

0.00

AC:

AN:

2068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000680

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

0.22

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.0031

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.49

M_CAP

Benign

0.039

MetaRNN

Benign

0.074

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

0.76

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

0.17

REVEL

Benign

0.020

Sift

Benign

0.27

Sift4G

Benign

0.14

Polyphen

0.098

Vest4

0.14

MVP

0.093

MPC

1.4

ClinPred

0.11

GERP RS

1.9

PromoterAI

-0.038

Neutral

(source)

Varity_R

0.061

gMVP

0.46

Mutation Taster

=93/7

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