chr12-16363776-T-C

Variant names:

• chr12-16363776-T-C
• rs3759207
• NM_020300.5:c.222-19T>C

Variant summary

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

The NM_001414356.1(MGST1):​c.212-3T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 1,568,612 control chromosomes in the GnomAD database, including 72,714 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.29 (6386 hom., cov: 32)
  • Exomes 𝑓: 0.30 (66328 hom.)
• Consequence: MGST1 NM_001414356.1 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.89
• Publications: 13 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001414356.1. 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.222-19T>C		intron	N/A	NP_064696.1	P10620-1
	MGST1	NM_001414355.1		c.237-19T>C		intron	N/A	NP_001401284.1
	MGST1	NM_001414356.1		c.212-3T>C		splice_region intron	N/A	NP_001401285.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGST1	ENST00000396210.8	TSL:1 MANE Select	c.222-19T>C		intron	N/A	ENSP00000379513.3	P10620-1
	MGST1	ENST00000396207.1	TSL:1	c.222-19T>C		intron	N/A	ENSP00000379510.1	P10620-1
	MGST1	ENST00000535309.5	TSL:1	c.221+6077T>C		intron	N/A	ENSP00000438308.1	P10620-2

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43437 AN: 151898 Hom.: 6377 Cov.: 32

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.295

GnomAD2 exomes AF: 0.285 AC: 68103 AN: 239306 AF XY: 0.288

Gnomad AFR exome AF: 0.252

Gnomad AMR exome AF: 0.239

Gnomad ASJ exome AF: 0.267

Gnomad EAS exome AF: 0.244

Gnomad FIN exome AF: 0.259

Gnomad NFE exome AF: 0.312

Gnomad OTH exome AF: 0.285

GnomAD4 exome AF: 0.303 AC: 429269 AN: 1416596 Hom.: 66328 Cov.: 29 AF XY: 0.303 AC XY: 212098 AN XY: 700384

African (AFR) AF: 0.256 AC: 8252 AN: 32292

American (AMR) AF: 0.240 AC: 9928 AN: 41406

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 6412 AN: 24412

East Asian (EAS) AF: 0.208 AC: 8108 AN: 39068

South Asian (SAS) AF: 0.294 AC: 24004 AN: 81714

European-Finnish (FIN) AF: 0.257 AC: 13436 AN: 52332

Middle Eastern (MID) AF: 0.266 AC: 1477 AN: 5550

European-Non Finnish (NFE) AF: 0.315 AC: 340190 AN: 1081580

Other (OTH) AF: 0.300 AC: 17462 AN: 58242

GnomAD4 genome AF: 0.286 AC: 43475 AN: 152016 Hom.: 6386 Cov.: 32 AF XY: 0.284 AC XY: 21134 AN XY: 74298

African (AFR) AF: 0.254 AC: 10528 AN: 41434

American (AMR) AF: 0.285 AC: 4359 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 952 AN: 3468

East Asian (EAS) AF: 0.241 AC: 1242 AN: 5164

South Asian (SAS) AF: 0.298 AC: 1434 AN: 4818

European-Finnish (FIN) AF: 0.261 AC: 2761 AN: 10580

Middle Eastern (MID) AF: 0.312 AC: 91 AN: 292

European-Non Finnish (NFE) AF: 0.312 AC: 21202 AN: 67968

Other (OTH) AF: 0.298 AC: 630 AN: 2112

Alfa AF: 0.297 Hom.: 6775

Bravo AF: 0.283

Asia WGS AF: 0.286 AC: 994 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.036
DANN	Benign	0.44
PhyloP100		-2.9
Mutation Taster		=11/89	disease causing

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: rs3759207; hg19: chr12-16516710; COSMIC: COSV50566454;