1-165649842-C-T

Position:

chr1-165649842-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_004528.4(MGST3):c.-6C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0376 in 1,613,906 control chromosomes in the GnomAD database, including 1,251 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

Frequency

Genomes: 𝑓 0.034 ( 94 hom., cov: 32)

Exomes 𝑓: 0.038 ( 1157 hom. )

Consequence

MGST3
NM_004528.4 5_prime_UTR_premature_start_codon_gain

Scores

Splicing: ADA: 0.00003323

Clinical Significance

association no assertion criteria provided O:1

Conservation

PhyloP100: 0.499

Variant links:

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 links:

MGST3 (HGNC:):

MGST3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022738874).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0341 (5198/152234) while in subpopulation NFE AF= 0.0408 (2778/68014). AF 95% confidence interval is 0.0396. There are 94 homozygotes in gnomad4. There are 2579 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 94 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MGST3	NM_004528.4 linkuse as main transcript	c.-6C>T		5_prime_UTR_premature_start_codon_gain_variant	2/6	ENST00000367889.8	NP_004519.1	O14880A0A024R8Z1
MGST3	NM_004528.4 linkuse as main transcript	c.-6C>T		splice_region_variant	2/6	ENST00000367889.8	NP_004519.1	O14880A0A024R8Z1
MGST3	NM_004528.4 linkuse as main transcript	c.-6C>T		5_prime_UTR_variant	2/6	ENST00000367889.8	NP_004519.1	O14880A0A024R8Z1
MGST3	XM_047421030.1 linkuse as main transcript	c.37C>T	p.Arg13Cys	missense_variant, splice_region_variant	3/7		XP_047276986.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MGST3	ENST00000367889 linkuse as main transcript	c.-6C>T		5_prime_UTR_premature_start_codon_gain_variant	2/6	1	NM_004528.4	ENSP00000356864.3	O14880
MGST3	ENST00000367884 linkuse as main transcript	c.-6C>T		5_prime_UTR_premature_start_codon_gain_variant	3/7	3		ENSP00000356859.1	O14880
MGST3	ENST00000367889.8 linkuse as main transcript	c.-6C>T		splice_region_variant	2/6	1	NM_004528.4	ENSP00000356864.3	O14880
MGST3	ENST00000367883.3 linkuse as main transcript	c.37C>T	p.Arg13Cys	missense_variant, splice_region_variant	3/7	3		ENSP00000356858.1	Q5VV89
MGST3	ENST00000367885.5 linkuse as main transcript	c.37C>T	p.Arg13Cys	missense_variant, splice_region_variant	3/7	2		ENSP00000356860.1	Q5VV89
MGST3	ENST00000367884.6 linkuse as main transcript	c.-6C>T		splice_region_variant	3/7	3		ENSP00000356859.1	O14880
MGST3	ENST00000367889 linkuse as main transcript	c.-6C>T		5_prime_UTR_variant	2/6	1	NM_004528.4	ENSP00000356864.3	O14880
MGST3	ENST00000367884 linkuse as main transcript	c.-6C>T		5_prime_UTR_variant	3/7	3		ENSP00000356859.1	O14880

Frequencies

GnomAD3 genomes

AF:

0.0342

AC:

5197

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0273

Gnomad AMI

AF:

0.109

Gnomad AMR

AF:

0.0279

Gnomad ASJ

AF:

0.0115

Gnomad EAS

AF:

0.00443

Gnomad SAS

AF:

0.0244

Gnomad FIN

AF:

0.0473

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0408

Gnomad OTH

AF:

0.0315

GnomAD3 exomes

AF:

0.0309

AC:

7779

AN:

251476

Hom.:

146

AF XY:

0.0321

AC XY:

4362

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.0257

Gnomad AMR exome

AF:

0.0167

Gnomad ASJ exome

AF:

0.0115

Gnomad EAS exome

AF:

0.00625

Gnomad SAS exome

AF:

0.0307

Gnomad FIN exome

AF:

0.0460

Gnomad NFE exome

AF:

0.0390

Gnomad OTH exome

AF:

0.0292

GnomAD4 exome

AF:

0.0380

AC:

55559

AN:

1461672

Hom.:

1157

Cov.:

AF XY:

0.0378

AC XY:

27465

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.0272

Gnomad4 AMR exome

AF:

0.0181

Gnomad4 ASJ exome

AF:

0.0122

Gnomad4 EAS exome

AF:

0.00615

Gnomad4 SAS exome

AF:

0.0306

Gnomad4 FIN exome

AF:

0.0433

Gnomad4 NFE exome

AF:

0.0414

Gnomad4 OTH exome

AF:

0.0347

GnomAD4 genome

AF:

0.0341

AC:

5198

AN:

152234

Hom.:

Cov.:

AF XY:

0.0346

AC XY:

2579

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0274

Gnomad4 AMR

AF:

0.0279

Gnomad4 ASJ

AF:

0.0115

Gnomad4 EAS

AF:

0.00444

Gnomad4 SAS

AF:

0.0240

Gnomad4 FIN

AF:

0.0473

Gnomad4 NFE

AF:

0.0408

Gnomad4 OTH

AF:

0.0312

Alfa

AF:

0.0355

Hom.:

261

Bravo

AF:

0.0324

TwinsUK

AF:

0.0415

AC:

154

ALSPAC

AF:

0.0394

AC:

152

ESP6500AA

AF:

0.0281

AC:

124

ESP6500EA

AF:

0.0379

AC:

326

ExAC

AF:

0.0307

AC:

3723

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.0406

EpiControl

AF:

0.0402

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.52

CADD

Benign

5.9

DANN

Benign

0.94

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.47

.;.;T

MetaRNN

Benign

0.0023

T;T;T

MetaSVM

Benign

-1.0

PROVEAN

Benign

-0.22

N;N;.

REVEL

Benign

0.047

Sift

Uncertain

0.013

D;D;.

Sift4G

Benign

0.095

T;T;T

Polyphen

0.0090

B;B;B

Vest4

0.061

ClinPred

0.0014

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000033

dbscSNV1_RF

Benign

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over