11-18137498-G-A

Position:

• chr11-18137498-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001370464.1(MRGPRX3):​c.296G>A​(p.Ser99Asn) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MRGPRX3 NM_001370464.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.18

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 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=0.055592686).
• BP6: Variant 11-18137498-G-A is Benign according to our data. Variant chr11-18137498-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2287446.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRGPRX3	NM_001370464.1	c.296G>A	p.Ser99Asn	missense_variant	2/2	ENST00000621697.2	NP_001357393.1
MRGPRX3	NM_054031.4	c.296G>A	p.Ser99Asn	missense_variant	3/3		NP_473372.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRGPRX3	ENST00000621697.2	c.296G>A	p.Ser99Asn	missense_variant	2/2	2	NM_001370464.1	ENSP00000481943.1
MRGPRX3	ENST00000396275.2	c.296G>A	p.Ser99Asn	missense_variant	3/3	1		ENSP00000379571.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 04, 2022

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	0.12
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.063
DANN	Benign	0.75
DEOGEN2	Benign	0.0020	T;.;T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.0049	N
LIST_S2	Benign	0.067	.;T;T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.056	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.080	N;.;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.32	N;N;.
REVEL	Benign	0.032
Sift	Benign	0.33	T;T;.
Sift4G	Benign	0.31	T;T;T
Polyphen		0.0	B;.;B
Vest4		0.048
MutPred		0.31		Gain of methylation at K96 (P = 0.0794);Gain of methylation at K96 (P = 0.0794);Gain of methylation at K96 (P = 0.0794);
MVP		0.22
MPC		0.043
ClinPred		0.25	T
GERP RS		-2.7
Varity_R		0.045
gMVP		0.13

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-18159045;