Variant chr11-18934484-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001393578.1(MRGPRX1):c.301G>A(p.Val101Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,610,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 35)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

MRGPRX1
NM_001393578.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.68

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10696009).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRGPRX1	NM_001393578.1 link	c.301G>A	p.Val101Met	missense_variant	2/2	ENST00000526914.2	NP_001380507.1
MRGPRX1	NM_147199.4 link	c.301G>A	p.Val101Met	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.301G>A	p.Val101Met	missense_variant	2/2	3	NM_001393578.1	ENSP00000499076.2		Q96LB2A0A494C1K4
MRGPRX1	ENST00000302797.4 link	c.301G>A	p.Val101Met	missense_variant	1/1	6		ENSP00000305766.3		Q96LB2

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151364

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000727

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459248

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725938

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:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151364

Hom.:

Cov.:

AF XY:

0.0000271

AC XY:

AN XY:

73882

show subpopulations

Gnomad4 AFR

AF:

0.0000727

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

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

Dec 19, 2023

The c.301G>A (p.V101M) alteration is located in exon 1 (coding exon 1) of the MRGPRX1 gene. This alteration results from a G to A substitution at nucleotide position 301, causing the valine (V) at amino acid position 101 to be replaced by a methionine (M). 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

0.13

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

8.0

DANN

Uncertain

0.99

DEOGEN2

Benign

0.015

Eigen

Benign

-0.83

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0073

LIST_S2

Benign

0.44

M_CAP

Benign

0.0061

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.99

MutationAssessor

Benign

2.0

PrimateAI

Benign

0.23

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.033

Sift

Benign

0.063

Sift4G

Benign

0.12

Polyphen

0.73

Vest4

0.11

MVP

0.23

MPC

0.055

ClinPred

0.18

GERP RS

0.28

Varity_R

0.12

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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