Genetic Variant MGST3:c.-7-2921C>T (chr1-165646920-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004528.4(MGST3):c.-7-2921C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,246 control chromosomes in the GnomAD database, including 7,126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

Frequency

Genomes: 𝑓 0.28 ( 7122 hom., cov: 33)

Exomes 𝑓: 0.29 ( 4 hom. )

Consequence

MGST3
NM_004528.4 intron

Scores

Clinical Significance

association no assertion criteria provided O:1

Conservation

PhyloP100: -0.784

Publications

12 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

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.-7-2921C>T		intron	N/A	NP_004519.1	O14880

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MGST3	ENST00000367889.8	TSL:1 MANE Select	c.-7-2921C>T	intron	N/A	ENSP00000356864.3	O14880
MGST3	ENST00000367883.3	TSL:3	c.36-2921C>T	intron	N/A	ENSP00000356858.1	Q5VV89
MGST3	ENST00000367885.5	TSL:2	c.36-2921C>T	intron	N/A	ENSP00000356860.1	Q5VV89

Frequencies

GnomAD3 genomes

AF:

0.283

AC:

43097

AN:

152034

Hom.:

7119

Cov.:

show subpopulations

Gnomad AFR

AF:

0.443

Gnomad AMI

AF:

0.249

Gnomad AMR

AF:

0.185

Gnomad ASJ

AF:

0.168

Gnomad EAS

AF:

0.0214

Gnomad SAS

AF:

0.121

Gnomad FIN

AF:

0.232

Gnomad MID

AF:

0.236

Gnomad NFE

AF:

0.256

Gnomad OTH

AF:

0.254

GnomAD4 exome

AF:

0.287

AC:

AN:

Hom.:

Cov.:

AF XY:

0.309

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.321

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.283

AC:

43120

AN:

152152

Hom.:

7122

Cov.:

AF XY:

0.276

AC XY:

20518

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.442

AC:

18357

AN:

41496

American (AMR)

AF:

0.184

AC:

2816

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.168

AC:

583

AN:

3472

East Asian (EAS)

AF:

0.0214

AC:

111

AN:

5182

South Asian (SAS)

AF:

0.121

AC:

585

AN:

4830

European-Finnish (FIN)

AF:

0.232

AC:

2456

AN:

10584

Middle Eastern (MID)

AF:

0.233

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.256

AC:

17388

AN:

67986

Other (OTH)

AF:

0.250

AC:

529

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1505

3010

4516

6021

7526

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

410

820

1230

1640

2050

<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:

0.256

Hom.:

20348

Bravo

AF:

0.286

Asia WGS

AF:

0.0910

AC:

317

AN:

3478

ClinVar

ClinVar submissions

Significance:association

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Pulmonary disease, chronic obstructive, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.1

(source)

DANN

Benign

0.83

PhyloP100

-0.78

Mutation Taster

=100/0

polymorphism (auto)

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over