Variant 1-165632229-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PVS1_ModerateBA1

The ENST00000367885.5(MGST3):c.-9-2G>A variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 1,610,452 control chromosomes in the GnomAD database, including 318,698 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as association (no stars).

Frequency

Genomes: 𝑓 0.58 ( 26822 hom., cov: 32)

Exomes 𝑓: 0.63 ( 291876 hom. )

Consequence

MGST3
ENST00000367885.5 splice_acceptor, intron

Scores

Clinical Significance

association no assertion criteria provided O:1

Conservation

PhyloP100: -0.147

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.08582834 fraction of the gene. Cryptic splice site detected, with MaxEntScore 9, offset of 0 (no position change), new splice context is: aactttaattccttccctAGgga. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MGST3	NM_004528.4 linkuse as main transcript	c.-8+936G>A		intron_variant		ENST00000367889.8	NP_004519.1	O14880A0A024R8Z1
MGST3	XM_047421030.1 linkuse as main transcript	c.-9-2G>A		splice_acceptor_variant, intron_variant			XP_047276986.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
MGST3	ENST00000367889.8 linkuse as main transcript	c.-8+936G>A	intron_variant	1	NM_004528.4	ENSP00000356864.3	O14880
MGST3	ENST00000367883.3 linkuse as main transcript	c.-9-2G>A	splice_acceptor_variant, intron_variant	3		ENSP00000356858.1	Q5VV89
MGST3	ENST00000367885.5 linkuse as main transcript	c.-9-2G>A	splice_acceptor_variant, intron_variant	2		ENSP00000356860.1	Q5VV89
MGST3	ENST00000367884.6 linkuse as main transcript	c.-104+937G>A	intron_variant	3		ENSP00000356859.1	O14880

Frequencies

GnomAD3 genomes

AF:

0.577

AC:

87662

AN:

151994

Hom.:

26802

Cov.:

show subpopulations

Gnomad AFR

AF:

0.378

Gnomad AMI

AF:

0.739

Gnomad AMR

AF:

0.672

Gnomad ASJ

AF:

0.738

Gnomad EAS

AF:

0.970

Gnomad SAS

AF:

0.794

Gnomad FIN

AF:

0.630

Gnomad MID

AF:

0.652

Gnomad NFE

AF:

0.611

Gnomad OTH

AF:

0.614

GnomAD3 exomes

AF:

0.673

AC:

162575

AN:

241404

Hom.:

56869

AF XY:

0.677

AC XY:

89677

AN XY:

132560

show subpopulations

Gnomad AFR exome

AF:

0.365

Gnomad AMR exome

AF:

0.752

Gnomad ASJ exome

AF:

0.736

Gnomad EAS exome

AF:

0.975

Gnomad SAS exome

AF:

0.773

Gnomad FIN exome

AF:

0.628

Gnomad NFE exome

AF:

0.616

Gnomad OTH exome

AF:

0.653

GnomAD4 exome

AF:

0.626

AC:

913255

AN:

1458340

Hom.:

291876

Cov.:

AF XY:

0.632

AC XY:

458347

AN XY:

725536

show subpopulations

Gnomad4 AFR exome

AF:

0.356

Gnomad4 AMR exome

AF:

0.744

Gnomad4 ASJ exome

AF:

0.730

Gnomad4 EAS exome

AF:

0.978

Gnomad4 SAS exome

AF:

0.770

Gnomad4 FIN exome

AF:

0.622

Gnomad4 NFE exome

AF:

0.603

Gnomad4 OTH exome

AF:

0.637

GnomAD4 genome

AF:

0.577

AC:

87711

AN:

152112

Hom.:

26822

Cov.:

AF XY:

0.586

AC XY:

43540

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.377

Gnomad4 AMR

AF:

0.672

Gnomad4 ASJ

AF:

0.738

Gnomad4 EAS

AF:

0.970

Gnomad4 SAS

AF:

0.794

Gnomad4 FIN

AF:

0.630

Gnomad4 NFE

AF:

0.611

Gnomad4 OTH

AF:

0.618

Alfa

AF:

0.623

Hom.:

44663

Bravo

AF:

0.572

Asia WGS

AF:

0.836

AC:

2909

AN:

3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Pulmonary disease, chronic obstructive, susceptibility to

Other:1

association, no assertion criteria provided

research

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Jul 05, 2022

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

9.3

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.20

Position offset: 45

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