rs6686643

Positions:

• chr1-165647351-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.9).
• 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/exons	MANE	Protein	UniProt
MGST3	NM_004528.4	c.-7-2490T>C		intron_variant		ENST00000367889.8	NP_004519.1
MGST3	XM_047421030.1	c.36-2490T>C		intron_variant			XP_047276986.1

Ensembl

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

Gnomad4 NFE exome AF: 0.00

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

Gnomad4 AFR AF: 0.447

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.0214

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.253

Gnomad4 OTH AF: 0.250

Alfa AF: 0.249 Hom.: 7507

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

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: rs6686643; hg19: chr1-165616588;