rs1042669

Variant names:

• chr12-16364098-T-G
• rs1042669
• NM_020300.5:c.*57T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020300.5(MGST1):​c.*57T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0424 in 1,521,860 control chromosomes in the GnomAD database, including 5,158 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as protective (no stars).

• Frequency:
  • Genomes: 𝑓 0.097 (1345 hom., cov: 33)
  • Exomes 𝑓: 0.036 (3813 hom.)
• Consequence: MGST1 NM_020300.5 3_prime_UTR
• Clinical Significance: protective no assertion criteria provided B:1
• Conservation: PhyloP100: 0.536
• Publications: 9 publications found

Genes affected

MGST1 (HGNC:7061): (microsomal glutathione S-transferase 1) The MAPEG (Membrane Associated Proteins in Eicosanoid and Glutathione metabolism) family consists of six human proteins, two of which are involved in the production of leukotrienes and prostaglandin E, important mediators of inflammation. Other family members, demonstrating glutathione S-transferase and peroxidase activities, are involved in cellular defense against toxic, carcinogenic, and pharmacologically active electrophilic compounds. This gene encodes a protein that catalyzes the conjugation of glutathione to electrophiles and the reduction of lipid hydroperoxides. This protein is localized to the endoplasmic reticulum and outer mitochondrial membrane where it is thought to protect these membranes from oxidative stress. Several transcript variants, some non-protein coding and some protein coding, have been found for this gene. [provided by RefSeq, May 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020300.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGST1	NM_020300.5	MANE Select	c.*57T>G		3_prime_UTR	Exon 4 of 4	NP_064696.1	P10620-1
	MGST1	NM_001414355.1		c.*57T>G		3_prime_UTR	Exon 4 of 4	NP_001401284.1
	MGST1	NM_001414356.1		c.*57T>G		3_prime_UTR	Exon 4 of 4	NP_001401285.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGST1	ENST00000396210.8	TSL:1 MANE Select	c.*57T>G		3_prime_UTR	Exon 4 of 4	ENSP00000379513.3	P10620-1
	MGST1	ENST00000396207.1	TSL:1	c.*57T>G		3_prime_UTR	Exon 4 of 4	ENSP00000379510.1	P10620-1
	MGST1	ENST00000535309.5	TSL:1	c.221+6399T>G		intron	N/A	ENSP00000438308.1	P10620-2

Frequencies

GnomAD3 genomes AF: 0.0973 AC: 14794 AN: 152114 Hom.: 1341 Cov.: 33

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.0925

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0496

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0134

Gnomad OTH AF: 0.0933

GnomAD4 exome AF: 0.0363 AC: 49742 AN: 1369628 Hom.: 3813 Cov.: 32 AF XY: 0.0365 AC XY: 24548 AN XY: 672920

African (AFR) AF: 0.215 AC: 6608 AN: 30678

American (AMR) AF: 0.210 AC: 6872 AN: 32790

Ashkenazi Jewish (ASJ) AF: 0.0952 AC: 1978 AN: 20784

East Asian (EAS) AF: 0.267 AC: 10390 AN: 38970

South Asian (SAS) AF: 0.0908 AC: 6374 AN: 70226

European-Finnish (FIN) AF: 0.0518 AC: 2541 AN: 49056

Middle Eastern (MID) AF: 0.0666 AC: 351 AN: 5270

European-Non Finnish (NFE) AF: 0.0105 AC: 11227 AN: 1065666

Other (OTH) AF: 0.0605 AC: 3401 AN: 56188

GnomAD4 genome AF: 0.0973 AC: 14809 AN: 152232 Hom.: 1345 Cov.: 33 AF XY: 0.101 AC XY: 7482 AN XY: 74428

African (AFR) AF: 0.206 AC: 8548 AN: 41512

American (AMR) AF: 0.145 AC: 2210 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0925 AC: 321 AN: 3472

East Asian (EAS) AF: 0.277 AC: 1435 AN: 5172

South Asian (SAS) AF: 0.102 AC: 491 AN: 4822

European-Finnish (FIN) AF: 0.0496 AC: 526 AN: 10610

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0134 AC: 909 AN: 68034

Other (OTH) AF: 0.0961 AC: 203 AN: 2112

Alfa AF: 0.0421 Hom.: 1386

Bravo AF: 0.112

Asia WGS AF: 0.211 AC: 735 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: protective

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Pulmonary disease, chronic obstructive, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.0
DANN	Benign	0.81
PhyloP100		0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1042669; hg19: chr12-16517032;