Variant 1-9105547-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_024980.5(GPR157):c.731G>A(p.Arg244Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000582 in 1,599,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000062 ( 0 hom. )

Consequence

GPR157
NM_024980.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.98

Variant links:

Genes affected

GPR157 (HGNC:23687): (G protein-coupled receptor 157) Predicted to enable G protein-coupled receptor activity. Predicted to be involved in positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway and radial glial cell differentiation. Predicted to be located in ciliary membrane. [provided by Alliance of Genome Resources, Apr 2022]

GPR157 links:

GPR157 (HGNC:):

GPR157 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.831

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR157	NM_024980.5 linkuse as main transcript	c.731G>A	p.Arg244Gln	missense_variant	3/4	ENST00000377411.5	NP_079256.4	Q5UAW9
GPR157	XM_005263496.6 linkuse as main transcript	c.692G>A	p.Arg231Gln	missense_variant	3/4		XP_005263553.1
GPR157	XM_005263497.6 linkuse as main transcript	c.598-913G>A		intron_variant			XP_005263554.1
GPR157	XR_007063977.1 linkuse as main transcript	n.806G>A		non_coding_transcript_exon_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR157	ENST00000377411.5 linkuse as main transcript	c.731G>A	p.Arg244Gln	missense_variant	3/4	1	NM_024980.5	ENSP00000366628.4		Q5UAW9
GPR157	ENST00000465853.1 linkuse as main transcript	c.94-913G>A		intron_variant		5		ENSP00000468362.1		K7ERQ3

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152198

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:

0.000193

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

GnomAD3 exomes

AF:

0.0000582

AC:

AN:

223408

Hom.:

AF XY:

0.0000417

AC XY:

AN XY:

119940

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000612

Gnomad SAS exome

AF:

0.0000369

Gnomad FIN exome

AF:

0.000105

Gnomad NFE exome

AF:

0.0000594

Gnomad OTH exome

AF:

0.000541

GnomAD4 exome

AF:

0.0000615

AC:

AN:

1446922

Hom.:

Cov.:

AF XY:

0.0000585

AC XY:

AN XY:

717984

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000409

Gnomad4 SAS exome

AF:

0.000108

Gnomad4 FIN exome

AF:

0.0000571

Gnomad4 NFE exome

AF:

0.0000217

Gnomad4 OTH exome

AF:

0.0000834

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000217

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000412

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 25, 2023

The c.731G>A (p.R244Q) alteration is located in exon 3 (coding exon 3) of the GPR157 gene. This alteration results from a G to A substitution at nucleotide position 731, causing the arginine (R) at amino acid position 244 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.72

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

0.10

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.20

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.046

MetaRNN

Pathogenic

0.83

MetaSVM

Uncertain

-0.23

MutationAssessor

Uncertain

2.1

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-2.2

REVEL

Uncertain

0.55

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.040

Polyphen

1.0

Vest4

0.92

MVP

0.36

MPC

0.47

ClinPred

0.32

GERP RS

4.7

Varity_R

0.60

gMVP

0.82

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over