11-18934206-C-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001393578.1(MRGPRX1):c.579G>T(p.Gly193=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00179 in 1,607,712 control chromosomes in the GnomAD database, including 129 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0022 (9 hom., cov: 35)
  • Exomes 𝑓: 0.0017 (120 hom.)
• Consequence: MRGPRX1 NM_001393578.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.684

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 11-18934206-C-A is Benign according to our data. Variant chr11-18934206-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2641673.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRGPRX1	NM_001393578.1	c.579G>T	p.Gly193=	synonymous_variant	2/2	ENST00000526914.2
MRGPRX1	NM_147199.4	c.579G>T	p.Gly193=	synonymous_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRGPRX1	ENST00000526914.2	c.579G>T	p.Gly193=	synonymous_variant	2/2	3	NM_001393578.1	P1
MRGPRX1	ENST00000302797.4	c.579G>T	p.Gly193=	synonymous_variant	1/1			P1

Frequencies

GnomAD3 genomes AF: 0.00223 AC: 336 AN: 150852 Hom.: 9 Cov.: 35

Gnomad AFR AF: 0.000754

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.00526

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000190

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00296

Gnomad OTH AF: 0.00484

GnomAD3 exomes AF: 0.000576 AC: 144 AN: 250194 Hom.: 5 AF XY: 0.000458 AC XY: 62 AN XY: 135246

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.00149

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.000707

Gnomad OTH exome AF: 0.000983

GnomAD4 exome AF: 0.00175 AC: 2548 AN: 1456742 Hom.: 120 Cov.: 37 AF XY: 0.00180 AC XY: 1305 AN XY: 724788

Gnomad4 AFR exome AF: 0.000359

Gnomad4 AMR exome AF: 0.00368

Gnomad4 ASJ exome AF: 0.000153

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000139

Gnomad4 FIN exome AF: 0.000281

Gnomad4 NFE exome AF: 0.00200

Gnomad4 OTH exome AF: 0.00199

GnomAD4 genome AF: 0.00223 AC: 336 AN: 150970 Hom.: 9 Cov.: 35 AF XY: 0.00222 AC XY: 164 AN XY: 73782

Gnomad4 AFR AF: 0.000752

Gnomad4 AMR AF: 0.00526

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000190

Gnomad4 NFE AF: 0.00296

Gnomad4 OTH AF: 0.00478

Alfa AF: 0.00180 Hom.: 4

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

MRGPRX1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	7.9
Dann	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.21		Position offset: -6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs147288525; hg19: chr11-18955753;