1-9104633-C-T

Position:

chr1-9104633-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_024980.5(GPR157):c.794G>A(p.Gly265Asp) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000314 in 1,589,972 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

GPR157
NM_024980.5 missense, splice_region

Scores

Splicing: ADA: 0.9073

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.78

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.862

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR157	NM_024980.5 linkuse as main transcript	c.794G>A	p.Gly265Asp	missense_variant, splice_region_variant	4/4	ENST00000377411.5	NP_079256.4	Q5UAW9
GPR157	XM_005263496.6 linkuse as main transcript	c.755G>A	p.Gly252Asp	missense_variant, splice_region_variant	4/4		XP_005263553.1
GPR157	XM_005263497.6 linkuse as main transcript	c.599G>A	p.Gly200Asp	missense_variant, splice_region_variant	3/3		XP_005263554.1
GPR157	XR_007063977.1 linkuse as main transcript	n.869G>A		splice_region_variant, non_coding_transcript_exon_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR157	ENST00000377411.5 linkuse as main transcript	c.794G>A	p.Gly265Asp	missense_variant, splice_region_variant	4/4	1	NM_024980.5	ENSP00000366628.4		Q5UAW9
GPR157	ENST00000465853.1 linkuse as main transcript	c.95G>A	p.Gly32Asp	missense_variant, splice_region_variant	2/2	5		ENSP00000468362.1		K7ERQ3

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152022

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000137

AC:

AN:

218714

Hom.:

AF XY:

0.0000169

AC XY:

AN XY:

118046

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000313

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000278

AC:

AN:

1437950

Hom.:

Cov.:

AF XY:

0.00000421

AC XY:

AN XY:

712744

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000364

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152022

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74234

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

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

Apr 15, 2024

The c.794G>A (p.G265D) alteration is located in exon 4 (coding exon 4) of the GPR157 gene. This alteration results from a G to A substitution at nucleotide position 794, causing the glycine (G) at amino acid position 265 to be replaced by an aspartic acid (D). 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

0.98

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Pathogenic

0.16

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.89

M_CAP

Uncertain

0.093

MetaRNN

Pathogenic

0.86

MetaSVM

Benign

-0.74

MutationAssessor

Uncertain

2.8

PrimateAI

Pathogenic

0.89

PROVEAN

Uncertain

-2.9

REVEL

Uncertain

0.48

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.92

MVP

0.58

MPC

0.50

ClinPred

0.92

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.75

gMVP

0.93

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.91

dbscSNV1_RF

Pathogenic

0.76

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