11-18934569-G-C
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_001393578.1(MRGPRX1):c.216C>G(p.Asp72Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000064 in 1,609,620 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 35)
Exomes 𝑓: 0.000067 ( 4 hom. )
Consequence
MRGPRX1
NM_001393578.1 missense
NM_001393578.1 missense
Scores
4
8
7
Clinical Significance
Conservation
PhyloP100: 2.72
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.75
BS2
?
High Homozygotes in GnomAdExome at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MRGPRX1 | NM_001393578.1 | c.216C>G | p.Asp72Glu | missense_variant | 2/2 | ENST00000526914.2 | |
MRGPRX1 | NM_147199.4 | c.216C>G | p.Asp72Glu | missense_variant | 1/1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MRGPRX1 | ENST00000526914.2 | c.216C>G | p.Asp72Glu | missense_variant | 2/2 | 3 | NM_001393578.1 | P1 | |
MRGPRX1 | ENST00000302797.4 | c.216C>G | p.Asp72Glu | missense_variant | 1/1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000330 AC: 5AN: 151498Hom.: 0 Cov.: 35
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GnomAD3 exomes AF: 0.000120 AC: 30AN: 249348Hom.: 2 AF XY: 0.000156 AC XY: 21AN XY: 134770
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GnomAD4 exome AF: 0.0000672 AC: 98AN: 1458122Hom.: 4 Cov.: 48 AF XY: 0.0000979 AC XY: 71AN XY: 725326
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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 | Jan 22, 2024 | The c.216C>G (p.D72E) alteration is located in exon 1 (coding exon 1) of the MRGPRX1 gene. This alteration results from a C to G substitution at nucleotide position 216, causing the aspartic acid (D) at amino acid position 72 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Loss of MoRF binding (P = 0.4691);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at