NM_001370464.1:c.241A>G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001370464.1(MRGPRX3):​c.241A>G​(p.Ile81Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000062 in 1,614,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000062 ( 0 hom. )

Consequence

MRGPRX3
NM_001370464.1 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.93
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.027724952).
BP6
Variant 11-18137443-A-G is Benign according to our data. Variant chr11-18137443-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3397942.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MRGPRX3NM_001370464.1 linkc.241A>G p.Ile81Val missense_variant Exon 2 of 2 ENST00000621697.2 NP_001357393.1
MRGPRX3NM_054031.4 linkc.241A>G p.Ile81Val missense_variant Exon 3 of 3 NP_473372.3 Q96LB0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MRGPRX3ENST00000621697.2 linkc.241A>G p.Ile81Val missense_variant Exon 2 of 2 2 NM_001370464.1 ENSP00000481943.1 Q96LB0
MRGPRX3ENST00000396275.2 linkc.241A>G p.Ile81Val missense_variant Exon 3 of 3 1 ENSP00000379571.2 Q96LB0

Frequencies

GnomAD3 genomes
AF:
0.0000592
AC:
9
AN:
152106
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00135
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251474
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135908
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000622
AC:
91
AN:
1461894
Hom.:
0
Cov.:
30
AF XY:
0.0000536
AC XY:
39
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00194
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000117
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000591
AC:
9
AN:
152224
Hom.:
0
Cov.:
32
AF XY:
0.0000806
AC XY:
6
AN XY:
74418
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00135
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000227
ExAC
AF:
0.0000165
AC:
2
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Jul 10, 2024
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.54
T
BayesDel_noAF
Benign
-0.78
CADD
Benign
0.032
DANN
Benign
0.30
DEOGEN2
Benign
0.0018
T;.;T
Eigen
Benign
-1.8
Eigen_PC
Benign
-1.9
FATHMM_MKL
Benign
0.016
N
LIST_S2
Benign
0.28
.;T;T
M_CAP
Benign
0.00070
T
MetaRNN
Benign
0.028
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.1
L;.;L
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-0.17
N;N;.
REVEL
Benign
0.0040
Sift
Benign
0.53
T;T;.
Sift4G
Benign
0.64
T;T;T
Polyphen
0.0010
B;.;B
Vest4
0.018
MutPred
0.36
Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);
MVP
0.085
MPC
0.040
ClinPred
0.028
T
GERP RS
-2.9
Varity_R
0.029
gMVP
0.051

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.

Other links and lift over

dbSNP: rs201803239; hg19: chr11-18158990; COSMIC: COSV66933568; COSMIC: COSV66933568; API