Genetic Variant NM_001370464.1:c.52C>T (chr11-18137254-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001370464.1(MRGPRX3):c.52C>T(p.Arg18Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000312 in 1,613,516 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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. R18P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 1 hom. )

Consequence

MRGPRX3
NM_001370464.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.699

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 made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006473094).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRGPRX3	NM_001370464.1 link	c.52C>T	p.Arg18Cys	missense_variant	Exon 2 of 2	ENST00000621697.2	NP_001357393.1
MRGPRX3	NM_054031.4 link	c.52C>T	p.Arg18Cys	missense_variant	Exon 3 of 3		NP_473372.3	Q96LB0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRGPRX3	ENST00000621697.2 link	c.52C>T	p.Arg18Cys	missense_variant	Exon 2 of 2	2	NM_001370464.1	ENSP00000481943.1		Q96LB0
MRGPRX3	ENST00000396275.2 link	c.52C>T	p.Arg18Cys	missense_variant	Exon 3 of 3	1		ENSP00000379571.2		Q96LB0

Frequencies

GnomAD3 genomes

AF:

0.00143

AC:

217

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00493

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000514

AC:

129

AN:

250734

Hom.:

AF XY:

0.000436

AC XY:

AN XY:

135456

show subpopulations

Gnomad AFR exome

AF:

0.00547

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00290

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000655

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000441

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000196

AC:

287

AN:

1461324

Hom.:

Cov.:

AF XY:

0.000169

AC XY:

123

AN XY:

726936

show subpopulations

Gnomad4 AFR exome

AF:

0.00532

Gnomad4 AMR exome

AF:

0.0000895

Gnomad4 ASJ exome

AF:

0.00238

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000162

Gnomad4 OTH exome

AF:

0.000331

GnomAD4 genome

AF:

0.00143

AC:

217

AN:

152192

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

113

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.00491

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000991

Hom.:

Bravo

AF:

0.00163

ESP6500AA

AF:

0.00432

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000593

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0016

T;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0069

LIST_S2

Benign

0.26

.;T;T

M_CAP

Benign

0.0014

MetaRNN

Benign

0.0065

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;.;L

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.89

N;N;.

REVEL

Benign

0.15

Sift

Benign

0.035

D;D;.

Sift4G

Uncertain

0.054

T;T;T

Polyphen

0.94

P;.;P

Vest4

0.15

MVP

0.014

MPC

0.17

ClinPred

0.075

GERP RS

-4.0

Varity_R

0.066

gMVP

0.10

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over