Variant 1-165654282-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_004528.4(MGST3):c.253A>G(p.Ile85Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,790 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 Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MGST3
NM_004528.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.27

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:

MGST3 (HGNC:):

MGST3 links:

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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=0.09538701).

BP6

Variant 1-165654282-A-G is Benign according to our data. Variant chr1-165654282-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2489817.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MGST3	NM_004528.4 linkuse as main transcript	c.253A>G	p.Ile85Val	missense_variant	5/6	ENST00000367889.8	NP_004519.1	O14880A0A024R8Z1
MGST3	XM_047421030.1 linkuse as main transcript	c.295A>G	p.Ile99Val	missense_variant	6/7		XP_047276986.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MGST3	ENST00000367889.8 linkuse as main transcript	c.253A>G	p.Ile85Val	missense_variant	5/6	1	NM_004528.4	ENSP00000356864.3	O14880
MGST3	ENST00000367883.3 linkuse as main transcript	c.295A>G	p.Ile99Val	missense_variant	6/7	3		ENSP00000356858.1	Q5VV89
MGST3	ENST00000367885.5 linkuse as main transcript	c.295A>G	p.Ile99Val	missense_variant	6/7	2		ENSP00000356860.1	Q5VV89
MGST3	ENST00000367884.6 linkuse as main transcript	c.253A>G	p.Ile85Val	missense_variant	6/7	3		ENSP00000356859.1	O14880

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251490

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

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:

0.00000137

AC:

AN:

1461790

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 27, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.0080

DANN

Benign

0.71

DEOGEN2

Benign

0.051

T;.;.;T;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.68

.;T;.;T;.;T

M_CAP

Benign

0.0044

MetaRNN

Benign

0.095

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.33

N;.;.;N;.;.

PrimateAI

Benign

0.42

PROVEAN

Benign

0.040

N;N;N;N;N;.

REVEL

Benign

0.058

Sift

Benign

0.64

T;T;T;T;T;.

Sift4G

Benign

0.68

T;T;T;T;T;T

Polyphen

0.0

B;.;B;B;B;B

Vest4

0.18

MutPred

0.58

.;.;Gain of catalytic residue at I99 (P = 0.0225);.;Gain of catalytic residue at I99 (P = 0.0225);Gain of catalytic residue at I99 (P = 0.0225);

MVP

0.12

MPC

0.34

ClinPred

0.013

GERP RS

-5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.018

gMVP

0.45

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over