dbSNP rs553515910: MRGPRX3:p.Asp2Asn (chr11-18137206-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001370464.1(MRGPRX3):c.4G>A(p.Asp2Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,435,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D2H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

MRGPRX3
NM_001370464.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.148

Publications

0 publications found

Variant links:

Genes affected

MRGPRX3 (HGNC:17980): (MAS related GPR family member X3) This gene encodes a member of the mas-related/sensory neuron specific subfamily of G protein coupled receptors. The encoded protein may be involved in sensory neuron regulation and in the modulation of pain. [provided by RefSeq, Oct 2009]

MRGPRX3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10576382).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370464.1. 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
	MRGPRX3	NM_001370464.1	MANE Select	c.4G>A	p.Asp2Asn	missense	Exon 2 of 2	NP_001357393.1	Q96LB0
	MRGPRX3	NM_054031.4		c.4G>A	p.Asp2Asn	missense	Exon 3 of 3	NP_473372.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRGPRX3	ENST00000621697.2	TSL:2 MANE Select	c.4G>A	p.Asp2Asn	missense	Exon 2 of 2	ENSP00000481943.1	Q96LB0
	MRGPRX3	ENST00000396275.2	TSL:1	c.4G>A	p.Asp2Asn	missense	Exon 3 of 3	ENSP00000379571.2	Q96LB0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.97e-7

AC:

AN:

1435070

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

710066

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32960

American (AMR)

AF:

0.00

AC:

AN:

43032

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24334

East Asian (EAS)

AF:

0.00

AC:

AN:

39366

South Asian (SAS)

AF:

0.00

AC:

AN:

82070

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52506

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5634

European-Non Finnish (NFE)

AF:

9.12e-7

AC:

AN:

1095954

Other (OTH)

AF:

0.00

AC:

AN:

59214

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

CADD

Benign

4.9

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0061

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.36

M_CAP

Benign

0.0017

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

PhyloP100

-0.15

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.7

REVEL

Benign

0.017

Sift

Benign

0.18

Sift4G

Benign

0.31

Polyphen

0.39

Vest4

0.060

MutPred

0.41

Loss of glycosylation at S3 (P = 0.1353)

MVP

0.030

MPC

0.053

ClinPred

0.13

GERP RS

1.0

Varity_R

0.055

gMVP

0.049

Mutation Taster

=89/11

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over