chr1-165651030-G-A
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_004528.4(MGST3):c.134G>A(p.Ser45Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
MGST3
NM_004528.4 missense
NM_004528.4 missense
Scores
4
9
6
Clinical Significance
Conservation
PhyloP100: 8.87
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 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.78
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MGST3 | NM_004528.4 | c.134G>A | p.Ser45Asn | missense_variant | 3/6 | ENST00000367889.8 | NP_004519.1 | |
MGST3 | XM_047421030.1 | c.176G>A | p.Ser59Asn | missense_variant | 4/7 | XP_047276986.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MGST3 | ENST00000367889.8 | c.134G>A | p.Ser45Asn | missense_variant | 3/6 | 1 | NM_004528.4 | ENSP00000356864.3 | ||
MGST3 | ENST00000367883.3 | c.176G>A | p.Ser59Asn | missense_variant | 4/7 | 3 | ENSP00000356858.1 | |||
MGST3 | ENST00000367885.5 | c.176G>A | p.Ser59Asn | missense_variant | 4/7 | 2 | ENSP00000356860.1 | |||
MGST3 | ENST00000367884.6 | c.134G>A | p.Ser45Asn | missense_variant | 4/7 | 3 | ENSP00000356859.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251488Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135914
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461874Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 727240
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
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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 | May 30, 2024 | The c.134G>A (p.S45N) alteration is located in exon 3 (coding exon 2) of the MGST3 gene. This alteration results from a G to A substitution at nucleotide position 134, causing the serine (S) at amino acid position 45 to be replaced by an asparagine (N). 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
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.;.;T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D;.;D;.;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
M;.;.;M;.;.
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N;.
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;D;.
Sift4G
Uncertain
D;D;D;D;D;D
Polyphen
D;.;D;D;D;D
Vest4
MutPred
0.46
.;.;Loss of glycosylation at S59 (P = 0.0449);.;Loss of glycosylation at S59 (P = 0.0449);Loss of glycosylation at S59 (P = 0.0449);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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Calibrated prediction
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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