rs745811592

Variant names:

• chr11-18934139-C-T
• rs745811592
• NM_001393578.1:c.646G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-18934139-C-T
• chr11-18934139-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001393578.1(MRGPRX1):​c.646G>A​(p.Val216Met) 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 1,459,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: MRGPRX1 NM_001393578.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.06
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14690164).

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.646G>A	p.Val216Met	missense	Exon 2 of 2	NP_001380507.1	Q96LB2
	MRGPRX1	NM_147199.4		c.646G>A	p.Val216Met	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.646G>A	p.Val216Met	missense	Exon 2 of 2	ENSP00000499076.2	Q96LB2
	MRGPRX1	ENST00000302797.4	TSL:6	c.646G>A	p.Val216Met	missense	Exon 1 of 1	ENSP00000305766.3	Q96LB2
	ENSG00000255244	ENST00000836338.1		n.374-5166C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD2 exomes AF: 0.00000798 AC: 2 AN: 250726 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1459412 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726010

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

American (AMR) AF: 0.00 AC: 0 AN: 44304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

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

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86036

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53354

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

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110430

Other (OTH) AF: 0.00 AC: 0 AN: 60316

GnomAD4 genome Cov.: 35

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000825 AC: 1

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	0.18
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.065	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-1.1
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.10
Sift	Uncertain	0.028	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.065
MutPred		0.53		Gain of helix (P = 0.0425)
MVP		0.17
MPC		0.11
ClinPred		0.76	D
GERP RS		-1.1
Varity_R		0.078
gMVP		0.058
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: rs745811592; hg19: chr11-18955686; COSMIC: COSV57107399; COSMIC: COSV57107399;