Genetic Variant NM_001170880.2:c.386G>C (chr11-64286993-G-C) – 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_001170880.2(GPR137):c.386G>C(p.Arg129Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,564 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. R129Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

GPR137
NM_001170880.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.766

Publications

0 publications found

Variant links:

Genes affected

GPR137 (HGNC:24300): (G protein-coupled receptor 137) Predicted to be involved in several processes, including negative regulation of bone resorption; negative regulation of osteoclast differentiation; and positive regulation of TORC1 signaling. Located in lysosomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

GPR137 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=0.19016954).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR137	NM_001170880.2 link	c.386G>C	p.Arg129Pro	missense_variant	Exon 2 of 7	ENST00000438980.7	NP_001164351.1	Q96N19-2Q9NQC5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR137	ENST00000438980.7 link	c.386G>C	p.Arg129Pro	missense_variant	Exon 2 of 7	1	NM_001170880.2	ENSP00000415698.2		Q96N19-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461564

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727060

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53178

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111956

Other (OTH)

AF:

0.0000166

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.012

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.044

.;.;.;.;.;.;.;.;.;.;T;.;.

Eigen

Benign

-0.063

Eigen_PC

Benign

0.023

FATHMM_MKL

Benign

0.71

LIST_S2

Uncertain

0.90

D;D;D;D;D;D;D;D;D;D;D;T;T

M_CAP

Benign

0.0088

MetaRNN

Benign

0.19

T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

.;.;N;.;.;N;.;.;.;N;N;.;.

PhyloP100

0.77

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.95

N;N;N;D;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.094

Sift

Benign

0.11

T;T;T;D;T;T;T;T;T;T;T;T;T

Sift4G

Benign

0.11

T;T;T;D;T;T;T;T;T;T;T;T;T

Polyphen

0.031

B;.;.;.;.;B;.;P;.;P;P;.;.

Vest4

0.67, 0.64, 0.65, 0.66, 0.66

MutPred

0.28

.;.;Loss of MoRF binding (P = 0.0072);.;Loss of MoRF binding (P = 0.0072);Loss of MoRF binding (P = 0.0072);Loss of MoRF binding (P = 0.0072);Loss of MoRF binding (P = 0.0072);Loss of MoRF binding (P = 0.0072);Loss of MoRF binding (P = 0.0072);Loss of MoRF binding (P = 0.0072);Loss of MoRF binding (P = 0.0072);Loss of MoRF binding (P = 0.0072);

MVP

0.29

MPC

1.6

ClinPred

0.71

GERP RS

3.0

PromoterAI

-0.030

Neutral

(source)

Varity_R

0.21

gMVP

0.65

Mutation Taster

=86/14

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over