chr1-165654279-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004528.4(MGST3):c.250C>T(p.Arg84Cys) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000161 in 1,613,834 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000096 ( 0 hom. )
Consequence
MGST3
NM_004528.4 missense, splice_region
NM_004528.4 missense, splice_region
Scores
3
9
6
Splicing: ADA: 0.9961
2
Clinical Significance
Conservation
PhyloP100: 4.65
Genes affected
MGST3 (HGNC:7064): (microsomal glutathione S-transferase 3) This gene encodes a member of the MAPEG (Membrane Associated Proteins in Eicosanoid and Glutathione metabolism) protein family. Members of this family are involved in the production of leukotrienes and prostaglandin E, important mediators of inflammation. This gene encodes an enzyme which catalyzes the conjugation of leukotriene A4 and reduced glutathione to produce leukotriene C4. This enzyme also demonstrates glutathione-dependent peroxidase activity towards lipid hydroperoxides.[provided by RefSeq, May 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MGST3 | NM_004528.4 | c.250C>T | p.Arg84Cys | missense_variant, splice_region_variant | 5/6 | ENST00000367889.8 | |
MGST3 | XM_047421030.1 | c.292C>T | p.Arg98Cys | missense_variant, splice_region_variant | 6/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MGST3 | ENST00000367889.8 | c.250C>T | p.Arg84Cys | missense_variant, splice_region_variant | 5/6 | 1 | NM_004528.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000789 AC: 12AN: 152032Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251488Hom.: 0 AF XY: 0.0000441 AC XY: 6AN XY: 135916
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GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461684Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727138
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GnomAD4 genome ? AF: 0.0000789 AC: 12AN: 152150Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5AN XY: 74374
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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 | Sep 14, 2023 | The c.250C>T (p.R84C) alteration is located in exon 5 (coding exon 4) of the MGST3 gene. This alteration results from a C to T substitution at nucleotide position 250, causing the arginine (R) at amino acid position 84 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;.;.;T;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.;M;.;.
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D;D;.
REVEL
Uncertain
Sift
Uncertain
D;T;T;D;T;.
Sift4G
Benign
T;T;T;T;T;T
Polyphen
D;.;P;D;P;P
Vest4
MutPred
0.59
.;.;Gain of catalytic residue at P97 (P = 0.0137);.;Gain of catalytic residue at P97 (P = 0.0137);Gain of catalytic residue at P97 (P = 0.0137);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at