rs6686643

Variant names:

• chr1-165647351-T-C
• rs6686643
• NM_004528.4:c.-7-2490T>C

Variant summary

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

The NM_004528.4(MGST3):​c.-7-2490T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,078 control chromosomes in the GnomAD database, including 7,151 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.28 (7151 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MGST3 NM_004528.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.503
• Publications: 13 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGST3	NM_004528.4	c.-7-2490T>C		intron_variant	Intron 1 of 5	ENST00000367889.8	NP_004519.1
MGST3	XM_047421030.1	c.36-2490T>C		intron_variant	Intron 2 of 6		XP_047276986.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGST3	ENST00000367889.8	c.-7-2490T>C		intron_variant	Intron 1 of 5	1	NM_004528.4	ENSP00000356864.3
MGST3	ENST00000367883.3	c.36-2490T>C		intron_variant	Intron 2 of 6	3		ENSP00000356858.1
MGST3	ENST00000367885.5	c.36-2490T>C		intron_variant	Intron 2 of 6	2		ENSP00000356860.1
MGST3	ENST00000367884.6	c.-7-2490T>C		intron_variant	Intron 2 of 6	3		ENSP00000356859.1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43078 AN: 151962 Hom.: 7146 Cov.: 32

Gnomad AFR AF: 0.447

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.0214

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.253

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.283 AC: 43103 AN: 152078 Hom.: 7151 Cov.: 32 AF XY: 0.276 AC XY: 20528 AN XY: 74336

African (AFR) AF: 0.447 AC: 18514 AN: 41430

American (AMR) AF: 0.185 AC: 2830 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 594 AN: 3466

East Asian (EAS) AF: 0.0214 AC: 111 AN: 5186

South Asian (SAS) AF: 0.122 AC: 588 AN: 4824

European-Finnish (FIN) AF: 0.232 AC: 2458 AN: 10574

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.253 AC: 17183 AN: 67980

Other (OTH) AF: 0.250 AC: 528 AN: 2114

Alfa AF: 0.262 Hom.: 12890

Bravo AF: 0.286

Asia WGS AF: 0.0910 AC: 317 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.47
PhyloP100		-0.50
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: rs6686643; hg19: chr1-165616588;