dbSNP rs777750722: GPR137C:p.Ala147Glu (chr14-52553587-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001099652.2(GPR137C):c.440C>A(p.Ala147Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000151 in 1,393,036 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. A147G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

GPR137C
NM_001099652.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.92

Publications

1 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 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPR137C	NM_001099652.2	MANE Select	c.440C>A	p.Ala147Glu	missense	Exon 1 of 7	NP_001093122.1	Q8N3F9
GPR137C	NM_001353361.2		c.440C>A	p.Ala147Glu	missense	Exon 1 of 8	NP_001340290.1
GPR137C	NR_148417.2		n.752C>A		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.440C>A	p.Ala147Glu	missense	Exon 1 of 7	ENSP00000315106.6	Q8N3F9
GPR137C	ENST00000542169.6	TSL:1	c.299C>A	p.Ala100Glu	missense	Exon 1 of 8	ENSP00000439165.2	H0YFL6
GPR137C	ENST00000866179.1		c.440C>A	p.Ala147Glu	missense	Exon 1 of 6	ENSP00000536238.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1393036

Hom.:

Cov.:

AF XY:

0.0000102

AC XY:

AN XY:

689256

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31290

American (AMR)

AF:

0.00

AC:

AN:

40124

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24808

East Asian (EAS)

AF:

0.00

AC:

AN:

35162

South Asian (SAS)

AF:

0.00

AC:

AN:

78896

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46534

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5608

European-Non Finnish (NFE)

AF:

0.0000186

AC:

AN:

1073260

Other (OTH)

AF:

0.0000174

AC:

AN:

57354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.87

BayesDel_addAF

Benign

-0.018

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

Eigen

Benign

0.097

Eigen_PC

Benign

0.031

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.035

MetaRNN

Uncertain

0.73

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

PhyloP100

4.9

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.22

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.0080

Polyphen

0.98

Vest4

0.73

MutPred

0.48

Gain of relative solvent accessibility (P = 0.09)

MVP

0.068

MPC

0.60

ClinPred

0.97

GERP RS

3.7

PromoterAI

0.019

Neutral

(source)

Varity_R

0.44

gMVP

0.84

Mutation Taster

=62/38

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