Genetic Variant NM_001099652.2:c.43G>T (chr14-52553190-G-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001099652.2(GPR137C):c.43G>T(p.Ala15Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000431 in 1,205,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

GPR137C
NM_001099652.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.114

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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.034783244).

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.43G>T	p.Ala15Ser	missense	Exon 1 of 7	NP_001093122.1	Q8N3F9
GPR137C	NM_001353361.2		c.43G>T	p.Ala15Ser	missense	Exon 1 of 8	NP_001340290.1
GPR137C	NR_148417.2		n.355G>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.43G>T	p.Ala15Ser	missense	Exon 1 of 7	ENSP00000315106.6	Q8N3F9
GPR137C	ENST00000866179.1		c.43G>T	p.Ala15Ser	missense	Exon 1 of 6	ENSP00000536238.1
TXNDC16	ENST00000936707.1		c.-182+153C>A		intron	N/A	ENSP00000606766.1

Frequencies

GnomAD3 genomes

AF:

0.000106

AC:

AN:

151086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000388

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000323

AC:

AN:

1054194

Hom.:

Cov.:

AF XY:

0.0000281

AC XY:

AN XY:

497830

show subpopulations

African (AFR)

AF:

0.000876

AC:

AN:

21698

American (AMR)

AF:

0.000269

AC:

AN:

7436

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13080

East Asian (EAS)

AF:

0.00

AC:

AN:

23384

South Asian (SAS)

AF:

0.00

AC:

AN:

19286

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20472

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

904494

Other (OTH)

AF:

0.000313

AC:

AN:

41576

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.544

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:

0.000119

AC:

AN:

151196

Hom.:

Cov.:

AF XY:

0.000190

AC XY:

AN XY:

73878

show subpopulations

African (AFR)

AF:

0.000435

AC:

AN:

41410

American (AMR)

AF:

0.00

AC:

AN:

15170

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5128

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10206

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67700

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000117

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

0.089

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.0031

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.34

M_CAP

Uncertain

0.091

MetaRNN

Benign

0.035

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

0.11

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

0.14

REVEL

Benign

0.035

Sift

Benign

0.69

Sift4G

Benign

0.91

Polyphen

0.050

Vest4

0.13

MutPred

0.14

Gain of glycosylation at A15 (P = 0.0012)

MVP

0.20

MPC

1.3

ClinPred

0.056

GERP RS

0.25

PromoterAI

-0.063

Neutral

(source)

Varity_R

0.042

gMVP

0.19

Mutation Taster

=98/2

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over