chr1-165651555-G-A

Position:

• chr1-165651555-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004528.4(MGST3):​c.192-423G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 297,952 control chromosomes in the GnomAD database, including 3,556 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency:
  • Genomes: 𝑓 0.15 (1864 hom., cov: 31)
  • Exomes 𝑓: 0.14 (1692 hom.)
• Consequence: MGST3 NM_004528.4 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -1.81

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MGST3	NM_004528.4	c.192-423G>A		intron_variant		ENST00000367889.8	NP_004519.1
MGST3	XM_047421030.1	c.234-423G>A		intron_variant			XP_047276986.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MGST3	ENST00000367889.8	c.192-423G>A		intron_variant		1	NM_004528.4	ENSP00000356864.3
MGST3	ENST00000367883.3	c.234-423G>A		intron_variant		3		ENSP00000356858.1
MGST3	ENST00000367885.5	c.234-423G>A		intron_variant		2		ENSP00000356860.1
MGST3	ENST00000367884.6	c.192-423G>A		intron_variant		3		ENSP00000356859.1

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22437 AN: 151958 Hom.: 1860 Cov.: 31

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.0643

Gnomad EAS AF: 0.0201

Gnomad SAS AF: 0.0548

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.146

GnomAD4 exome AF: 0.138 AC: 20190 AN: 145876 Hom.: 1692 Cov.: 0 AF XY: 0.131 AC XY: 10298 AN XY: 78576

Gnomad4 AFR exome AF: 0.142

Gnomad4 AMR exome AF: 0.0916

Gnomad4 ASJ exome AF: 0.0710

Gnomad4 EAS exome AF: 0.0164

Gnomad4 SAS exome AF: 0.0654

Gnomad4 FIN exome AF: 0.164

Gnomad4 NFE exome AF: 0.170

Gnomad4 OTH exome AF: 0.145

GnomAD4 genome AF: 0.148 AC: 22445 AN: 152076 Hom.: 1864 Cov.: 31 AF XY: 0.142 AC XY: 10575 AN XY: 74344

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.0643

Gnomad4 EAS AF: 0.0201

Gnomad4 SAS AF: 0.0548

Gnomad4 FIN AF: 0.158

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.144

Alfa AF: 0.164 Hom.: 3486

Bravo AF: 0.145

Asia WGS AF: 0.0500 AC: 174 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

Jul 05, 2022

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.48
DANN	Benign	0.43

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: rs11799886; hg19: chr1-165620792;