Variant 11-18934207-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001393578.1(MRGPRX1):c.578G>T(p.Gly193Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00181 in 1,607,740 control chromosomes in the GnomAD database, including 128 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. G193G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0022 ( 9 hom., cov: 35)

Exomes 𝑓: 0.0018 ( 119 hom. )

Consequence

MRGPRX1
NM_001393578.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.748

Variant links:

Genes affected

MRGPRX1 (HGNC:17962): (MAS related GPR family member X1) Enables transmembrane signaling receptor activity. Involved in cell surface receptor signaling pathway and response to chloroquine. Predicted to be located in cell surface. [provided by Alliance of Genome Resources, Apr 2022]

MRGPRX1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0075779557).

BP6

Variant 11-18934207-C-A is Benign according to our data. Variant chr11-18934207-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2641674.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRGPRX1	NM_001393578.1 linkuse as main transcript	c.578G>T	p.Gly193Val	missense_variant	2/2	ENST00000526914.2
MRGPRX1	NM_147199.4 linkuse as main transcript	c.578G>T	p.Gly193Val	missense_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRGPRX1	ENST00000526914.2 linkuse as main transcript	c.578G>T	p.Gly193Val	missense_variant	2/2	3	NM_001393578.1	P1
MRGPRX1	ENST00000302797.4 linkuse as main transcript	c.578G>T	p.Gly193Val	missense_variant	1/1			P1

Frequencies

GnomAD3 genomes

AF:

0.00224

AC:

338

AN:

150850

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000754

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.00534

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000190

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00296

Gnomad OTH

AF:

0.00532

GnomAD3 exomes

AF:

0.000576

AC:

144

AN:

250166

Hom.:

AF XY:

0.000458

AC XY:

AN XY:

135230

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00149

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.000707

Gnomad OTH exome

AF:

0.000983

GnomAD4 exome

AF:

0.00177

AC:

2573

AN:

1456772

Hom.:

119

Cov.:

AF XY:

0.00180

AC XY:

1305

AN XY:

724778

show subpopulations

Gnomad4 AFR exome

AF:

0.000359

Gnomad4 AMR exome

AF:

0.00368

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.000281

Gnomad4 NFE exome

AF:

0.00202

Gnomad4 OTH exome

AF:

0.00202

GnomAD4 genome

AF:

0.00224

AC:

338

AN:

150968

Hom.:

Cov.:

AF XY:

0.00222

AC XY:

164

AN XY:

73762

show subpopulations

Gnomad4 AFR

AF:

0.000752

Gnomad4 AMR

AF:

0.00533

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000190

Gnomad4 NFE

AF:

0.00296

Gnomad4 OTH

AF:

0.00526

Alfa

AF:

0.00178

Hom.:

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00156

AC:

ExAC

AF:

0.000124

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

MRGPRX1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.61

Cadd

Benign

7.8

Dann

Benign

0.62

DEOGEN2

Benign

0.049

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.0086

LIST_S2

Benign

0.67

M_CAP

Benign

0.0024

MetaRNN

Benign

0.0076

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.57

MutationTaster

Benign

1.0

PrimateAI

Benign

0.22

PROVEAN

Pathogenic

-6.0

REVEL

Benign

0.050

Sift

Benign

0.29

Sift4G

Benign

0.94

Polyphen

0.051

Vest4

0.14

MVP

0.24

MPC

0.043

ClinPred

0.034

GERP RS

-4.6

Varity_R

0.16

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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