1-165646920-C-T

Position:

• chr1-165646920-C-T

Variant summary

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

The NM_004528.4(MGST3):​c.-7-2921C>T 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 152,246 control chromosomes in the GnomAD database, including 7,126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency:
  • Genomes: 𝑓 0.28 (7122 hom., cov: 33)
  • Exomes 𝑓: 0.29 (4 hom.)
• Consequence: MGST3 NM_004528.4 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.784

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MGST3	NM_004528.4	c.-7-2921C>T		intron_variant		ENST00000367889.8	NP_004519.1
MGST3	XM_047421030.1	c.36-2921C>T		intron_variant			XP_047276986.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MGST3	ENST00000367889.8	c.-7-2921C>T		intron_variant		1	NM_004528.4	ENSP00000356864.3
MGST3	ENST00000367883.3	c.36-2921C>T		intron_variant		3		ENSP00000356858.1
MGST3	ENST00000367885.5	c.36-2921C>T		intron_variant		2		ENSP00000356860.1
MGST3	ENST00000367884.6	c.-7-2921C>T		intron_variant		3		ENSP00000356859.1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43097 AN: 152034 Hom.: 7119 Cov.: 33

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.0214

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.254

GnomAD4 exome AF: 0.287 AC: 27 AN: 94 Hom.: 4 Cov.: 0 AF XY: 0.309 AC XY: 21 AN XY: 68

Gnomad4 AFR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.321

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.283 AC: 43120 AN: 152152 Hom.: 7122 Cov.: 33 AF XY: 0.276 AC XY: 20518 AN XY: 74396

Gnomad4 AFR AF: 0.442

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.0214

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.250

Alfa AF: 0.246 Hom.: 8113

Bravo AF: 0.286

Asia WGS AF: 0.0910 AC: 317 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	-0.86
CADD	Benign	1.1
DANN	Benign	0.83

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: rs957644; hg19: chr1-165616157;