Genetic Variant MGST3:p.His82Tyr (chr1-165652030-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_004528.4(MGST3):c.244C>T(p.His82Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00013 in 1,612,188 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 1 hom. )

Consequence

MGST3
NM_004528.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.97

Publications

2 publications found

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]

MGST3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18985063).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004528.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGST3	NM_004528.4	MANE Select	c.244C>T	p.His82Tyr	missense	Exon 4 of 6	NP_004519.1	O14880

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MGST3	ENST00000367889.8	TSL:1 MANE Select	c.244C>T	p.His82Tyr	missense	Exon 4 of 6	ENSP00000356864.3	O14880
MGST3	ENST00000367883.3	TSL:3	c.286C>T	p.His96Tyr	missense	Exon 5 of 7	ENSP00000356858.1	Q5VV89
MGST3	ENST00000367885.5	TSL:2	c.286C>T	p.His96Tyr	missense	Exon 5 of 7	ENSP00000356860.1	Q5VV89

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

151896

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.000171

AC:

AN:

251448

AF XY:

0.000184

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000343

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000125

AC:

183

AN:

1460292

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

108

AN XY:

726610

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33450

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26114

East Asian (EAS)

AF:

0.00

AC:

AN:

39670

South Asian (SAS)

AF:

0.00

AC:

AN:

86226

European-Finnish (FIN)

AF:

0.000112

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000154

AC:

171

AN:

1110626

Other (OTH)

AF:

0.0000995

AC:

AN:

60316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000171

AC:

AN:

151896

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74154

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41330

American (AMR)

AF:

0.00

AC:

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10516

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000353

AC:

AN:

68010

Other (OTH)

AF:

0.000479

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000266

Hom.:

Bravo

AF:

0.000155

ExAC

AF:

0.000189

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.061

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.044

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.0064

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.30

PhyloP100

2.0

PrimateAI

Uncertain

0.57

PROVEAN

Benign

0.59

REVEL

Benign

0.17

Sift

Benign

0.91

Sift4G

Benign

1.0

Polyphen

0.0050

Vest4

0.45

MVP

0.50

MPC

0.47

ClinPred

0.075

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.081

gMVP

0.67

Mutation Taster

=82/18

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over