Genetic Variant MRGPRX1:p.Pro135Leu (chr11-18934381-G-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001393578.1(MRGPRX1):c.404C>T(p.Pro135Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000548 in 1,459,356 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 35)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

MRGPRX1
NM_001393578.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.64

Publications

0 publications found

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:

ENSG00000255244 (HGNC:):

ENSG00000255244 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.859

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393578.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRGPRX1	NM_001393578.1	MANE Select	c.404C>T	p.Pro135Leu	missense	Exon 2 of 2	NP_001380507.1	Q96LB2
	MRGPRX1	NM_147199.4		c.404C>T	p.Pro135Leu	missense	Exon 1 of 1	NP_671732.3	Q96LB2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MRGPRX1	ENST00000526914.2	TSL:3 MANE Select	c.404C>T	p.Pro135Leu	missense	Exon 2 of 2	ENSP00000499076.2	Q96LB2
MRGPRX1	ENST00000302797.4	TSL:6	c.404C>T	p.Pro135Leu	missense	Exon 1 of 1	ENSP00000305766.3	Q96LB2
ENSG00000255244	ENST00000836338.1		n.374-4924G>A		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000279

AC:

AN:

250708

AF XY:

0.00000738

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000204

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000548

AC:

AN:

1459356

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726010

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33456

American (AMR)

AF:

0.000135

AC:

AN:

44304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26100

East Asian (EAS)

AF:

0.00

AC:

AN:

39654

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86040

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53358

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110370

Other (OTH)

AF:

0.0000166

AC:

AN:

60314

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.406

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.34

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.073

Eigen

Uncertain

0.22

Eigen_PC

Benign

-0.028

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.85

M_CAP

Benign

0.0062

MetaRNN

Pathogenic

0.86

MetaSVM

Benign

-0.48

MutationAssessor

Uncertain

2.7

PhyloP100

4.6

PrimateAI

Benign

0.32

PROVEAN

Pathogenic

-10

REVEL

Benign

0.19

Sift

Benign

0.049

Sift4G

Uncertain

0.038

Polyphen

0.99

Vest4

0.34

MutPred

0.78

Gain of catalytic residue at P135 (P = 0.0461)

MVP

0.54

MPC

0.25

ClinPred

0.99

GERP RS

2.3

Varity_R

0.46

gMVP

0.46

Mutation Taster

=83/17

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over