chr4-139678591-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002413.5(MGST2):​c.107C>T​(p.Thr36Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000446 in 1,613,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

MGST2
NM_002413.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.715
Variant links:
Genes affected
MGST2 (HGNC:7063): (microsomal glutathione S-transferase 2) The MAPEG (Membrane Associated Proteins in Eicosanoid and Glutathione metabolism) family consists of six human proteins, several of which are involved in the production of leukotrienes and prostaglandin E, important mediators of inflammation. This gene encodes a protein which catalyzes the conjugation of leukotriene A4 and reduced glutathione to produce leukotriene C4. Alternatively spliced transcript variants encoding different isoforms have been identified in this gene. [provided by RefSeq, Feb 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.027950883).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MGST2NM_002413.5 linkuse as main transcriptc.107C>T p.Thr36Met missense_variant 2/5 ENST00000265498.6 NP_002404.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MGST2ENST00000265498.6 linkuse as main transcriptc.107C>T p.Thr36Met missense_variant 2/51 NM_002413.5 ENSP00000265498 P1Q99735-1

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152182
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000283
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000717
AC:
18
AN:
251194
Hom.:
0
AF XY:
0.0000737
AC XY:
10
AN XY:
135752
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000695
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000969
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000445
AC:
65
AN:
1461798
Hom.:
0
Cov.:
30
AF XY:
0.0000550
AC XY:
40
AN XY:
727196
show subpopulations
Gnomad4 AFR exome
AF:
0.000120
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.000421
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000187
Gnomad4 NFE exome
AF:
0.0000306
Gnomad4 OTH exome
AF:
0.0000993
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152182
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000283
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000291
Hom.:
0
Bravo
AF:
0.0000302
ExAC
AF:
0.0000659
AC:
8
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.000178

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 GeneticsDec 27, 2023The c.107C>T (p.T36M) alteration is located in exon 2 (coding exon 2) of the MGST2 gene. This alteration results from a C to T substitution at nucleotide position 107, causing the threonine (T) at amino acid position 36 to be replaced by a methionine (M). 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
Benign
0.062
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
0.057
DANN
Benign
0.80
DEOGEN2
Benign
0.028
T;T;.
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.0069
N
LIST_S2
Benign
0.46
.;T;T
M_CAP
Benign
0.025
T
MetaRNN
Benign
0.028
T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
-0.74
N;N;N
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-0.35
N;.;N
REVEL
Benign
0.052
Sift
Benign
0.21
T;.;T
Sift4G
Benign
0.16
T;T;T
Polyphen
0.0030
B;B;.
Vest4
0.19
MutPred
0.32
Loss of phosphorylation at T36 (P = 0.0449);Loss of phosphorylation at T36 (P = 0.0449);Loss of phosphorylation at T36 (P = 0.0449);
MVP
0.25
MPC
0.11
ClinPred
0.027
T
GERP RS
-6.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.011
gMVP
0.22

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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: rs762855354; hg19: chr4-140599745; API