chr1-165651030-G-A

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

Scores

4
9
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.87
Variant links:
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]

Genome browser will be placed here

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
MGST3NM_004528.4 linkuse as main transcriptc.134G>A p.Ser45Asn missense_variant 3/6 ENST00000367889.8 NP_004519.1 O14880A0A024R8Z1
MGST3XM_047421030.1 linkuse as main transcriptc.176G>A p.Ser59Asn missense_variant 4/7 XP_047276986.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MGST3ENST00000367889.8 linkuse as main transcriptc.134G>A p.Ser45Asn missense_variant 3/61 NM_004528.4 ENSP00000356864.3 O14880
MGST3ENST00000367883.3 linkuse as main transcriptc.176G>A p.Ser59Asn missense_variant 4/73 ENSP00000356858.1 Q5VV89
MGST3ENST00000367885.5 linkuse as main transcriptc.176G>A p.Ser59Asn missense_variant 4/72 ENSP00000356860.1 Q5VV89
MGST3ENST00000367884.6 linkuse as main transcriptc.134G>A p.Ser45Asn missense_variant 4/73 ENSP00000356859.1 O14880

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
251488
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135914
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000116
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:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461874
Hom.:
0
Cov.:
30
AF XY:
0.00000413
AC XY:
3
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000894
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

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 submitterclinical testingAmbry GeneticsMay 30, 2024The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.70
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.16
CADD
Pathogenic
28
DANN
Uncertain
0.99
DEOGEN2
Benign
0.18
T;.;.;T;.;.
Eigen
Uncertain
0.65
Eigen_PC
Uncertain
0.62
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.97
.;D;.;D;.;D
M_CAP
Benign
0.025
D
MetaRNN
Pathogenic
0.78
D;D;D;D;D;D
MetaSVM
Uncertain
-0.28
T
MutationAssessor
Pathogenic
3.3
M;.;.;M;.;.
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
-2.1
N;N;N;N;N;.
REVEL
Uncertain
0.35
Sift
Uncertain
0.0040
D;D;D;D;D;.
Sift4G
Uncertain
0.016
D;D;D;D;D;D
Polyphen
0.96
D;.;D;D;D;D
Vest4
0.83
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
0.74
MPC
1.1
ClinPred
0.90
D
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.94
gMVP
0.89

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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.

Other links and lift over

dbSNP: rs756881927; hg19: chr1-165620267; API