Variant 1-6249694-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000377893.3(GPR153):c.1474C>T(p.Arg492Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00316 in 1,044,024 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 7 hom. )

Consequence

GPR153
ENST00000377893.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0900

Variant links:

Genes affected

GPR153 (HGNC:23618): (G protein-coupled receptor 153) This gene encodes an integral membrane protein that belongs to the Class A rhodopsin superfamily of G protein coupled receptors. The encoded protein is expressed primarily in the central nervous system. A knockdown of the orthologous gene in rat is associated with a significant reduction in food intake and impaired decision making ability. Mutations in this gene are associated with schizophrenia, autism, and other neuropsychiatric disorders. The expression of this gene is activated by the glioma-associated oncogene homolog 1 transcription factor which, in turn, is activated by sonic hedgehog in normal and tumorigenic cells. [provided by RefSeq, Feb 2017]

GPR153 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015916944).

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GPR153	NM_207370.4 linkuse as main transcript	c.1474C>T	p.Arg492Cys	missense_variant	6/6	ENST00000377893.3	NP_997253.2
GPR153	XM_011541434.4 linkuse as main transcript	c.1474C>T	p.Arg492Cys	missense_variant	6/6		XP_011539736.1
GPR153	XM_017001250.2 linkuse as main transcript	c.1474C>T	p.Arg492Cys	missense_variant	5/5		XP_016856739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR153	ENST00000377893.3 linkuse as main transcript	c.1474C>T	p.Arg492Cys	missense_variant	6/6	1	NM_207370.4	ENSP00000367125	P1

Frequencies

GnomAD3 genomes

AF:

0.00147

AC:

216

AN:

147390

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000855

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000202

Gnomad ASJ

AF:

0.00206

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00255

Gnomad OTH

AF:

0.000981

GnomAD3 exomes

AF:

0.00435

AC:

AN:

230

Hom.:

AF XY:

0.00781

AC XY:

AN XY:

128

show subpopulations

Gnomad NFE exome

AF:

0.00442

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00344

AC:

3087

AN:

896526

Hom.:

Cov.:

AF XY:

0.00335

AC XY:

1404

AN XY:

419516

show subpopulations

Gnomad4 AFR exome

AF:

0.000352

Gnomad4 AMR exome

AF:

0.00162

Gnomad4 ASJ exome

AF:

0.00131

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000262

Gnomad4 NFE exome

AF:

0.00375

Gnomad4 OTH exome

AF:

0.00174

GnomAD4 genome

AF:

0.00146

AC:

216

AN:

147498

Hom.:

Cov.:

AF XY:

0.00118

AC XY:

AN XY:

71860

show subpopulations

Gnomad4 AFR

AF:

0.000852

Gnomad4 AMR

AF:

0.000202

Gnomad4 ASJ

AF:

0.00206

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00255

Gnomad4 OTH

AF:

0.000971

Alfa

AF:

0.00180

Hom.:

Bravo

AF:

0.00153

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 15, 2021

The c.1474C>T (p.R492C) alteration is located in exon 6 (coding exon 5) of the GPR153 gene. This alteration results from a C to T substitution at nucleotide position 1474, causing the arginine (R) at amino acid position 492 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

0.15

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.057

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.73

M_CAP

Pathogenic

0.60

MetaRNN

Benign

0.016

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-1.1

REVEL

Benign

0.015

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.015

Polyphen

0.013

Vest4

0.15

MVP

0.48

MPC

1.2

ClinPred

0.21

GERP RS

2.0

Varity_R

0.20

gMVP

0.63

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