NM_001370464.1:c.225C>A

Variant names:

• chr11-18137427-C-A
• rs777866935
• NM_001370464.1:c.225C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001370464.1(MRGPRX3):​c.225C>A​(p.Phe75Leu) 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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: MRGPRX3 NM_001370464.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.81
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2335335).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370464.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRGPRX3	NM_001370464.1	MANE Select	c.225C>A	p.Phe75Leu	missense	Exon 2 of 2	NP_001357393.1	Q96LB0
	MRGPRX3	NM_054031.4		c.225C>A	p.Phe75Leu	missense	Exon 3 of 3	NP_473372.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRGPRX3	ENST00000621697.2	TSL:2 MANE Select	c.225C>A	p.Phe75Leu	missense	Exon 2 of 2	ENSP00000481943.1	Q96LB0
	MRGPRX3	ENST00000396275.2	TSL:1	c.225C>A	p.Phe75Leu	missense	Exon 3 of 3	ENSP00000379571.2	Q96LB0

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	13
DANN	Benign	0.93
DEOGEN2	Benign	0.058	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.00082	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.8
PrimateAI	Benign	0.33	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Benign	0.027
Sift	Benign	0.046	D
Sift4G	Benign	0.12	T
Polyphen		0.34	B
Vest4		0.36
MutPred		0.43		Loss of catalytic residue at F75 (P = 0.0053)
MVP		0.23
MPC		0.073
ClinPred		0.76	D
GERP RS		0.49
Varity_R		0.24
gMVP		0.15
Mutation Taster		=83/17	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: rs777866935; hg19: chr11-18158974;