11-18137254-C-T

Variant names:

• chr11-18137254-C-T
• rs7932708
• NM_001370464.1:c.52C>T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001370464.1(MRGPRX3):​c.52C>T​(p.Arg18Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000312 in 1,613,516 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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. R18P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0014 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00020 (1 hom.)
• Consequence: MRGPRX3 NM_001370464.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.699

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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006473094).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRGPRX3	NM_001370464.1	c.52C>T	p.Arg18Cys	missense_variant	Exon 2 of 2	ENST00000621697.2	NP_001357393.1
MRGPRX3	NM_054031.4	c.52C>T	p.Arg18Cys	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.52C>T	p.Arg18Cys	missense_variant	Exon 2 of 2	2	NM_001370464.1	ENSP00000481943.1
MRGPRX3	ENST00000396275.2	c.52C>T	p.Arg18Cys	missense_variant	Exon 3 of 3	1		ENSP00000379571.2

Frequencies

GnomAD3 genomes AF: 0.00143 AC: 217 AN: 152074 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00493

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000514 AC: 129 AN: 250734 Hom.: 0 AF XY: 0.000436 AC XY: 59 AN XY: 135456

Gnomad AFR exome AF: 0.00547

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00290

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0000655

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000441

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000196 AC: 287 AN: 1461324 Hom.: 1 Cov.: 29 AF XY: 0.000169 AC XY: 123 AN XY: 726936

Gnomad4 AFR exome AF: 0.00532

Gnomad4 AMR exome AF: 0.0000895

Gnomad4 ASJ exome AF: 0.00238

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000162

Gnomad4 OTH exome AF: 0.000331

GnomAD4 genome AF: 0.00143 AC: 217 AN: 152192 Hom.: 1 Cov.: 32 AF XY: 0.00152 AC XY: 113 AN XY: 74416

Gnomad4 AFR AF: 0.00491

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.000991 Hom.: 0

Bravo AF: 0.00163

ESP6500AA AF: 0.00432 AC: 19

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000593 AC: 72

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0016	T;.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0069	N
LIST_S2	Benign	0.26	.;T;T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.0065	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;.;L
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.89	N;N;.
REVEL	Benign	0.15
Sift	Benign	0.035	D;D;.
Sift4G	Uncertain	0.054	T;T;T
Polyphen		0.94	P;.;P
Vest4		0.15
MVP		0.014
MPC		0.17
ClinPred		0.075	T
GERP RS		-4.0
Varity_R		0.066
gMVP		0.10

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

LitVar

Other links and lift over

dbSNP: rs7932708; hg19: chr11-18158801; COSMIC: COSV66934850; COSMIC: COSV66934850;