Variant 11-18174082-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_054032.3(MRGPRX4):c.826G>T(p.Gly276Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000632 in 1,614,148 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00040 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000028 ( 1 hom. )

Consequence

MRGPRX4
NM_054032.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.40

Variant links:

Genes affected

MRGPRX4 (HGNC:17617): (MAS related GPR family member X4) Predicted to enable G protein-coupled receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Predicted to act upstream of or within chemosensory behavior and hematopoietic progenitor cell differentiation. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

MRGPRX4 links:

ENSG00000255470 (HGNC:):

ENSG00000255470 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.112893194).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRGPRX4	NM_054032.3 link	c.826G>T	p.Gly276Cys	missense_variant	1/1	ENST00000314254.3	NP_473373.2	Q96LA9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRGPRX4	ENST00000314254.3 link	c.826G>T	p.Gly276Cys	missense_variant	1/1	6	NM_054032.3	ENSP00000314042.3		Q96LA9
ENSG00000255470	ENST00000527671.1 link	n.601+14813C>A		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000401

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00145

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:

0.000478

GnomAD3 exomes

AF:

0.0000676

AC:

AN:

251492

Hom.:

AF XY:

0.0000662

AC XY:

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.000984

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000280

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.000866

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.000401

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.000457

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00144

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:

0.000473

Alfa

AF:

0.0000297

Hom.:

Bravo

AF:

0.000329

ESP6500AA

AF:

0.000910

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000741

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 01, 2022

The c.826G>T (p.G276C) alteration is located in exon 1 (coding exon 1) of the MRGPRX4 gene. This alteration results from a G to T substitution at nucleotide position 826, causing the glycine (G) at amino acid position 276 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.69

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.024

Eigen

Uncertain

0.35

Eigen_PC

Benign

0.13

FATHMM_MKL

Benign

0.25

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.0015

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.86

MutationAssessor

Pathogenic

4.0

PrimateAI

Benign

0.31

PROVEAN

Pathogenic

-8.9

REVEL

Benign

0.16

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.45

MVP

0.61

MPC

0.70

ClinPred

0.62

GERP RS

2.9

Varity_R

0.84

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over