Variant 1-9105667-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024980.5(GPR157):c.611C>G(p.Ser204Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000249 in 1,610,384 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00026 ( 0 hom. )

Consequence

GPR157
NM_024980.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.87

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GPR157	NM_024980.5 linkuse as main transcript	c.611C>G	p.Ser204Cys	missense_variant	3/4	ENST00000377411.5
GPR157	XM_005263496.6 linkuse as main transcript	c.598-26C>G		intron_variant
GPR157	XM_005263497.6 linkuse as main transcript	c.598-1033C>G		intron_variant
GPR157	XR_007063977.1 linkuse as main transcript	n.686C>G		non_coding_transcript_exon_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR157	ENST00000377411.5 linkuse as main transcript	c.611C>G	p.Ser204Cys	missense_variant	3/4	1	NM_024980.5	P1
GPR157	ENST00000465853.1 linkuse as main transcript	c.96-1033C>G		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152194

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000103

AC:

AN:

242800

Hom.:

AF XY:

0.0000534

AC XY:

AN XY:

131150

show subpopulations

Gnomad AFR exome

AF:

0.0000635

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000105

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000211

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000265

AC:

386

AN:

1458190

Hom.:

Cov.:

AF XY:

0.000241

AC XY:

175

AN XY:

724982

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000388

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000340

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.0000986

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.0000672

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:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000200

Hom.:

Bravo

AF:

0.0000982

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000115

AC:

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

May 26, 2022

The c.611C>G (p.S204C) alteration is located in exon 3 (coding exon 3) of the GPR157 gene. This alteration results from a C to G substitution at nucleotide position 611, causing the serine (S) at amino acid position 204 to be replaced by a cysteine (C). 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

Benign

0.16

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.055

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.85

M_CAP

Benign

0.055

MetaRNN

Uncertain

0.64

MetaSVM

Benign

-0.87

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.1

REVEL

Benign

0.26

Sift

Benign

0.23

Sift4G

Uncertain

0.045

Polyphen

1.0

Vest4

0.70

MVP

0.24

MPC

0.40

ClinPred

0.32

GERP RS

4.8

Varity_R

0.092

gMVP

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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