Variant 11-18137250-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001370464.1(MRGPRX3):c.48C>A(p.Asn16Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000265 in 1,612,858 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00026 ( 0 hom. )

Consequence

MRGPRX3
NM_001370464.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.26

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02255705).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRGPRX3	NM_001370464.1 linkuse as main transcript	c.48C>A	p.Asn16Lys	missense_variant	2/2	ENST00000621697.2	NP_001357393.1
MRGPRX3	NM_054031.4 linkuse as main transcript	c.48C>A	p.Asn16Lys	missense_variant	3/3		NP_473372.3	Q96LB0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRGPRX3	ENST00000621697.2 linkuse as main transcript	c.48C>A	p.Asn16Lys	missense_variant	2/2	2	NM_001370464.1	ENSP00000481943.1		Q96LB0
MRGPRX3	ENST00000396275.2 linkuse as main transcript	c.48C>A	p.Asn16Lys	missense_variant	3/3	1		ENSP00000379571.2		Q96LB0

Frequencies

GnomAD3 genomes

AF:

0.000283

AC:

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000376

AC:

AN:

250226

Hom.:

AF XY:

0.000414

AC XY:

AN XY:

135174

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0000869

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00125

Gnomad NFE exome

AF:

0.000505

Gnomad OTH exome

AF:

0.000491

GnomAD4 exome

AF:

0.000263

AC:

384

AN:

1460760

Hom.:

Cov.:

AF XY:

0.000271

AC XY:

197

AN XY:

726608

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0000895

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00124

Gnomad4 NFE exome

AF:

0.000258

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.000283

AC:

AN:

152098

Hom.:

Cov.:

AF XY:

0.000310

AC XY:

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000381

Hom.:

Bravo

AF:

0.000234

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000582

AC:

ExAC

AF:

0.000445

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000297

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

Jun 17, 2024

The c.48C>A (p.N16K) alteration is located in exon 3 (coding exon 1) of the MRGPRX3 gene. This alteration results from a C to A substitution at nucleotide position 48, causing the asparagine (N) at amino acid position 16 to be replaced by a lysine (K). 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

0.15

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.75

CADD

Benign

4.7

DANN

Benign

0.69

DEOGEN2

Benign

0.039

T;.;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0030

LIST_S2

Benign

0.28

.;T;T

M_CAP

Benign

0.0013

MetaRNN

Benign

0.023

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

2.0

M;.;M

PrimateAI

Benign

0.28

PROVEAN

Pathogenic

-4.5

D;D;.

REVEL

Benign

0.031

Sift

Benign

0.050

D;T;.

Sift4G

Uncertain

0.0090

D;D;D

Polyphen

0.14

B;.;B

Vest4

0.060

MutPred

0.50

Gain of ubiquitination at N16 (P = 0.0069);Gain of ubiquitination at N16 (P = 0.0069);Gain of ubiquitination at N16 (P = 0.0069);

MVP

0.014

MPC

0.079

ClinPred

0.038

GERP RS

0.23

Varity_R

0.13

gMVP

0.078

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