rs8133

Positions:

• chr1-165655562-G-T

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MGST3	NM_004528.4	c.*58G>T		3_prime_UTR_variant	6/6	ENST00000367889.8	NP_004519.1
MGST3	XM_047421030.1	c.*58G>T		3_prime_UTR_variant	7/7		XP_047276986.1

Ensembl

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

Gnomad4 AFR exome AF: 0.124

Gnomad4 AMR exome AF: 0.241

Gnomad4 ASJ exome AF: 0.562

Gnomad4 EAS exome AF: 0.136

Gnomad4 SAS exome AF: 0.346

Gnomad4 FIN exome AF: 0.440

Gnomad4 NFE exome AF: 0.443

Gnomad4 OTH exome AF: 0.403

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

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.319

Gnomad4 ASJ AF: 0.565

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.329

Gnomad4 FIN AF: 0.441

Gnomad4 NFE AF: 0.447

Gnomad4 OTH AF: 0.374

Alfa AF: 0.431 Hom.: 24827

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

association, no assertion criteria provided

research

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

May 13, 2022

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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

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

Other links and lift over

dbSNP: rs8133; hg19: chr1-165624799;