rs8133

Variant names:

• chr1-165655562-G-T
• rs8133
• NM_004528.4:c.*58G>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004528.4(MGST3):​c.*58G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 1,600,950 control chromosomes in the GnomAD database, including 141,123 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency:
  • Genomes: 𝑓 0.34 (10184 hom., cov: 30)
  • Exomes 𝑓: 0.42 (130939 hom.)
• Consequence: MGST3 NM_004528.4 3_prime_UTR
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: 0.740
• Publications: 18 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGST3	NM_004528.4	c.*58G>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000367889.8	NP_004519.1
MGST3	XM_047421030.1	c.*58G>T		3_prime_UTR_variant	Exon 7 of 7		XP_047276986.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGST3	ENST00000367889.8	c.*58G>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_004528.4	ENSP00000356864.3
MGST3	ENST00000367883.3	c.*58G>T		3_prime_UTR_variant	Exon 7 of 7	3		ENSP00000356858.1
MGST3	ENST00000367885.5	c.*58G>T		3_prime_UTR_variant	Exon 7 of 7	2		ENSP00000356860.1
MGST3	ENST00000367884.6	c.*58G>T		3_prime_UTR_variant	Exon 7 of 7	3		ENSP00000356859.1

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51119 AN: 151488 Hom.: 10183 Cov.: 30

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.370

GnomAD4 exome AF: 0.416 AC: 603357 AN: 1449344 Hom.: 130939 Cov.: 27 AF XY: 0.417 AC XY: 300640 AN XY: 721192

African (AFR) AF: 0.124 AC: 4093 AN: 32936

American (AMR) AF: 0.241 AC: 10610 AN: 44100

Ashkenazi Jewish (ASJ) AF: 0.562 AC: 14624 AN: 26030

East Asian (EAS) AF: 0.136 AC: 5338 AN: 39370

South Asian (SAS) AF: 0.346 AC: 29535 AN: 85302

European-Finnish (FIN) AF: 0.440 AC: 23302 AN: 52944

Middle Eastern (MID) AF: 0.485 AC: 2671 AN: 5508

European-Non Finnish (NFE) AF: 0.443 AC: 489107 AN: 1103372

Other (OTH) AF: 0.403 AC: 24077 AN: 59782

GnomAD4 genome AF: 0.337 AC: 51120 AN: 151606 Hom.: 10184 Cov.: 30 AF XY: 0.335 AC XY: 24815 AN XY: 74010

African (AFR) AF: 0.133 AC: 5502 AN: 41318

American (AMR) AF: 0.319 AC: 4845 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1960 AN: 3466

East Asian (EAS) AF: 0.151 AC: 777 AN: 5160

South Asian (SAS) AF: 0.329 AC: 1574 AN: 4782

European-Finnish (FIN) AF: 0.441 AC: 4621 AN: 10476

Middle Eastern (MID) AF: 0.493 AC: 144 AN: 292

European-Non Finnish (NFE) AF: 0.447 AC: 30332 AN: 67904

Other (OTH) AF: 0.374 AC: 787 AN: 2102

Alfa AF: 0.406 Hom.: 36672

Bravo AF: 0.321

Asia WGS AF: 0.255 AC: 889 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Pulmonary disease, chronic obstructive, susceptibility to Other:1

May 13, 2022

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Significance: association

Review Status: no assertion criteria provided

Collection Method: research

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	12
DANN	Benign	0.87
PhyloP100		0.74
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8133; hg19: chr1-165624799;