rs1438441396

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr11-18137236-C-A
• chr11-18137236-C-G
• chr11-18137236-C-T

Variant summary

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

The NM_001370464.1(MRGPRX3):​c.34C>A​(p.Leu12Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,136 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. L12V) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: MRGPRX3 NM_001370464.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06244418).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRGPRX3	NM_001370464.1	c.34C>A	p.Leu12Met	missense_variant	Exon 2 of 2	ENST00000621697.2	NP_001357393.1
MRGPRX3	NM_054031.4	c.34C>A	p.Leu12Met	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.34C>A	p.Leu12Met	missense_variant	Exon 2 of 2	2	NM_001370464.1	ENSP00000481943.1
MRGPRX3	ENST00000396275.2	c.34C>A	p.Leu12Met	missense_variant	Exon 3 of 3	1		ENSP00000379571.2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152136 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152136 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74320

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.41
DANN	Benign	0.52
DEOGEN2	Benign	0.0029	T;.;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0048	N
LIST_S2	Benign	0.069	.;T;T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.062	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;.;M
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.16	N;N;.
REVEL	Benign	0.017
Sift	Benign	0.23	T;T;.
Sift4G	Benign	0.26	T;T;T
Polyphen		0.087	B;.;B
Vest4		0.13
MutPred		0.32		Loss of catalytic residue at L12 (P = 0.0688);Loss of catalytic residue at L12 (P = 0.0688);Loss of catalytic residue at L12 (P = 0.0688);
MVP		0.014
MPC		0.054
ClinPred		0.32	T
GERP RS		-4.0
Varity_R		0.047
gMVP		0.044

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1438441396; hg19: chr11-18158783;