chr11-18137236-C-G

Variant names:

• chr11-18137236-C-G
• rs1438441396
• NM_001370464.1:c.34C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001370464.1(MRGPRX3):​c.34C>G​(p.Leu12Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MRGPRX3 NM_001370464.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.88
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047446966).

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.34C>G	p.Leu12Val	missense	Exon 2 of 2	NP_001357393.1	Q96LB0
	MRGPRX3	NM_054031.4		c.34C>G	p.Leu12Val	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.34C>G	p.Leu12Val	missense	Exon 2 of 2	ENSP00000481943.1	Q96LB0
	MRGPRX3	ENST00000396275.2	TSL:1	c.34C>G	p.Leu12Val	missense	Exon 3 of 3	ENSP00000379571.2	Q96LB0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459188 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 725712

African (AFR) AF: 0.0000598 AC: 2 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44638

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25832

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 85780

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53306

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110422

Other (OTH) AF: 0.00 AC: 0 AN: 60298

GnomAD4 genome Cov.: 32

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	Benign	0.075
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.11
DANN	Benign	0.44
DEOGEN2	Benign	0.0043	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0054	N
LIST_S2	Benign	0.095	T
M_CAP	Benign	0.00094	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		-1.9
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.013
Sift	Benign	0.53	T
Sift4G	Benign	0.61	T
Polyphen		0.0010	B
Vest4		0.032
MutPred		0.29		Gain of glycosylation at T13 (P = 0.1025)
MVP		0.014
MPC		0.045
ClinPred		0.064	T
GERP RS		-4.0
Varity_R		0.026
gMVP		0.042
Mutation Taster		=98/2	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: rs1438441396; hg19: chr11-18158783;