Variant chr11-18934304-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_001393578.1(MRGPRX1):c.481T>C(p.Cys161Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,610,654 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 35)

Exomes 𝑓: 0.000015 ( 2 hom. )

Consequence

MRGPRX1
NM_001393578.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00100

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 Likely_benign. Variant got -2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.92

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRGPRX1	NM_001393578.1 link	c.481T>C	p.Cys161Arg	missense_variant	2/2	ENST00000526914.2	NP_001380507.1
MRGPRX1	NM_147199.4 link	c.481T>C	p.Cys161Arg	missense_variant	1/1		NP_671732.3	Q96LB2W8W3P5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRGPRX1	ENST00000526914.2 link	c.481T>C	p.Cys161Arg	missense_variant	2/2	3	NM_001393578.1	ENSP00000499076.2		Q96LB2A0A494C1K4
MRGPRX1	ENST00000302797.4 link	c.481T>C	p.Cys161Arg	missense_variant	1/1	6		ENSP00000305766.3		Q96LB2

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000399

AC:

AN:

250802

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135604

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:

0.0000927

Gnomad NFE exome

AF:

0.0000704

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1459434

Hom.:

Cov.:

AF XY:

0.00000689

AC XY:

AN XY:

726040

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:

0.0000187

Gnomad4 NFE exome

AF:

0.0000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151220

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73822

show subpopulations

Gnomad4 AFR

AF:

0.0000243

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:

0.0000148

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000102

Hom.:

ExAC

AF:

0.0000577

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Mar 20, 2024

The c.481T>C (p.C161R) alteration is located in exon 1 (coding exon 1) of the MRGPRX1 gene. This alteration results from a T to C substitution at nucleotide position 481, causing the cysteine (C) at amino acid position 161 to be replaced by an arginine (R). 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

Uncertain

0.49

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.090

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.42

M_CAP

Benign

0.015

MetaRNN

Pathogenic

0.92

MetaSVM

Benign

-0.62

MutationAssessor

Pathogenic

3.8

PrimateAI

Benign

0.31

PROVEAN

Pathogenic

-11

REVEL

Benign

0.21

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.28

MutPred

0.90

Loss of catalytic residue at M159 (P = 7e-04);

MVP

0.68

MPC

0.28

ClinPred

0.99

GERP RS

2.3

Varity_R

0.89

gMVP

0.53

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