11-18137352-G-C

Position:

• chr11-18137352-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001370464.1(MRGPRX3):​c.150G>C​(p.Trp50Cys) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MRGPRX3 NM_001370464.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.71

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.779

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRGPRX3	NM_001370464.1	c.150G>C	p.Trp50Cys	missense_variant	2/2	ENST00000621697.2	NP_001357393.1
MRGPRX3	NM_054031.4	c.150G>C	p.Trp50Cys	missense_variant	3/3		NP_473372.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRGPRX3	ENST00000621697.2	c.150G>C	p.Trp50Cys	missense_variant	2/2	2	NM_001370464.1	ENSP00000481943.1
MRGPRX3	ENST00000396275.2	c.150G>C	p.Trp50Cys	missense_variant	3/3	1		ENSP00000379571.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 29, 2021

The c.150G>C (p.W50C) alteration is located in exon 3 (coding exon 1) of the MRGPRX3 gene. This alteration results from a G to C substitution at nucleotide position 150, causing the tryptophan (W) at amino acid position 50 to be replaced by a cysteine (C). 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	0.33
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.075	T;.;T
Eigen	Benign	0.11
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.094	N
LIST_S2	Uncertain	0.86	.;D;D
M_CAP	Benign	0.0054	T
MetaRNN	Pathogenic	0.78	D;D;D
MetaSVM	Benign	-0.76	T
MutationAssessor	Pathogenic	3.6	H;.;H
PrimateAI	Benign	0.28	T
PROVEAN	Pathogenic	-12	D;D;.
REVEL	Benign	0.14
Sift	Uncertain	0.0070	D;D;.
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		0.98	D;.;D
Vest4		0.36
MutPred		0.75		Gain of catalytic residue at L51 (P = 0.0103);Gain of catalytic residue at L51 (P = 0.0103);Gain of catalytic residue at L51 (P = 0.0103);
MVP		0.099
MPC		0.32
ClinPred		1.0	D
GERP RS		1.5
Varity_R		0.56
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-18158899;