11-18137384-T-G

Variant names:

• chr11-18137384-T-G
• rs771149863
• NM_001370464.1:c.182T>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001370464.1(MRGPRX3):​c.182T>G​(p.Val61Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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. V61A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MRGPRX3 NM_001370464.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.831
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29724044).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRGPRX3	NM_001370464.1	c.182T>G	p.Val61Gly	missense_variant	Exon 2 of 2	ENST00000621697.2	NP_001357393.1
MRGPRX3	NM_054031.4	c.182T>G	p.Val61Gly	missense_variant	Exon 3 of 3		NP_473372.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRGPRX3	ENST00000621697.2	c.182T>G	p.Val61Gly	missense_variant	Exon 2 of 2	2	NM_001370464.1	ENSP00000481943.1
MRGPRX3	ENST00000396275.2	c.182T>G	p.Val61Gly	missense_variant	Exon 3 of 3	1		ENSP00000379571.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	18
DANN	Benign	0.84
DEOGEN2	Benign	0.044	T;.;T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.39	.;T;T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.30	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;.;L
PhyloP100		0.83
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-2.7	D;D;.
REVEL	Benign	0.056
Sift	Pathogenic	0.0	D;D;.
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.044	B;.;B
Vest4		0.094
MutPred		0.73		Loss of stability (P = 0.0038);Loss of stability (P = 0.0038);Loss of stability (P = 0.0038);
MVP		0.095
MPC		0.062
ClinPred		0.36	T
GERP RS		1.5
Varity_R		0.39
gMVP		0.15
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs771149863; hg19: chr11-18158931;