11-18934237-C-G

Variant names:

• chr11-18934237-C-G
• rs1173612248
• NM_001393578.1:c.548G>C

Variant summary

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

The NM_001393578.1(MRGPRX1):​c.548G>C​(p.Trp183Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,459,444 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 34)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: MRGPRX1 NM_001393578.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.502
• Publications: 0 publications found

Genes affected

MRGPRX1 (HGNC:17962): (MAS related GPR family member X1) Enables transmembrane signaling receptor activity. Involved in cell surface receptor signaling pathway and response to chloroquine. Predicted to be located in cell surface. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000255244 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393578.1. 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
	MRGPRX1	NM_001393578.1	MANE Select	c.548G>C	p.Trp183Ser	missense	Exon 2 of 2	NP_001380507.1	Q96LB2
	MRGPRX1	NM_147199.4		c.548G>C	p.Trp183Ser	missense	Exon 1 of 1	NP_671732.3	Q96LB2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRGPRX1	ENST00000526914.2	TSL:3 MANE Select	c.548G>C	p.Trp183Ser	missense	Exon 2 of 2	ENSP00000499076.2	Q96LB2
	MRGPRX1	ENST00000302797.4	TSL:6	c.548G>C	p.Trp183Ser	missense	Exon 1 of 1	ENSP00000305766.3	Q96LB2
	ENSG00000255244	ENST00000836338.1		n.374-5068C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1459444 Hom.: 0 Cov.: 37 AF XY: 0.00000275 AC XY: 2 AN XY: 726040

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33458

American (AMR) AF: 0.0000451 AC: 2 AN: 44304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39654

South Asian (SAS) AF: 0.00 AC: 0 AN: 86048

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53346

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110452

Other (OTH) AF: 0.00 AC: 0 AN: 60318

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000286652), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

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	0.20
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	20
DANN	Benign	0.76
DEOGEN2	Benign	0.086	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		-0.50
PrimateAI	Benign	0.29	T
PROVEAN	Pathogenic	-10	D
REVEL	Benign	0.062
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.29
MutPred		0.68		Gain of glycosylation at W183 (P = 0.1845)
MVP		0.23
MPC		0.22
ClinPred		0.59	D
GERP RS		0.25
Varity_R		0.55
gMVP		0.47
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: rs1173612248; hg19: chr11-18955784;