1-109737079-C-T

Position:

chr1-109737079-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000849.5(GSTM3):c.670G>A(p.Val224Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 1,599,424 control chromosomes in the GnomAD database, including 87,787 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.27 ( 6899 hom., cov: 33)

Exomes 𝑓: 0.32 ( 80888 hom. )

Consequence

GSTM3
NM_000849.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.69

Variant links:

Genes affected

GSTM3 (HGNC:4635): (glutathione S-transferase mu 3) Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. At present, eight distinct classes of the soluble cytoplasmic mammalian glutathione S-transferases have been identified: alpha, kappa, mu, omega, pi, sigma, theta and zeta. This gene encodes a glutathione S-transferase that belongs to the mu class. The mu class of enzymes functions in the detoxification of electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress, by conjugation with glutathione. The genes encoding the mu class of enzymes are organized in a gene cluster on chromosome 1p13.3 and are known to be highly polymorphic. These genetic variations can change an individual's susceptibility to carcinogens and toxins as well as affect the toxicity and efficacy of certain drugs. Mutations of this class mu gene have been linked with a slight increase in a number of cancers, likely due to exposure with environmental toxins. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2008]

GSTM3 links:

(HGNC:):

links:

GSTM5 (HGNC:4637): (glutathione S-transferase mu 5) Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. At present, eight distinct classes of the soluble cytoplasmic mammalian glutathione S-transferases have been identified: alpha, kappa, mu, omega, pi, sigma, theta and zeta. This gene encodes a glutathione S-transferase that belongs to the mu class. The mu class of enzymes functions in the detoxification of electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress, by conjugation with glutathione. The genes encoding the mu class of enzymes are organized in a gene cluster on chromosome 1p13.3 and are known to be highly polymorphic. These genetic variations can change an individual's susceptibility to carcinogens and toxins as well as affect the toxicity and efficacy of certain drugs. Diversification of these genes has occurred in regions encoding substrate-binding domains, as well as in tissue expression patterns, to accommodate an increasing number of foreign compounds. [provided by RefSeq, Jul 2008]

GSTM5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.3028056E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSTM3	NM_000849.5 linkuse as main transcript	c.670G>A	p.Val224Ile	missense_variant	9/9	ENST00000361066.7	NP_000840.2
GSTM3	NR_024537.2 linkuse as main transcript	n.904G>A		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSTM3	ENST00000361066.7 linkuse as main transcript	c.670G>A	p.Val224Ile	missense_variant	9/9	1	NM_000849.5	ENSP00000354357	P1
	ENST00000431955.1 linkuse as main transcript	n.565C>T		non_coding_transcript_exon_variant	3/4	3

Frequencies

GnomAD3 genomes

AF:

0.268

AC:

40816

AN:

152046

Hom.:

6894

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.189

Gnomad AMR

AF:

0.338

Gnomad ASJ

AF:

0.268

Gnomad EAS

AF:

0.745

Gnomad SAS

AF:

0.422

Gnomad FIN

AF:

0.288

Gnomad MID

AF:

0.283

Gnomad NFE

AF:

0.304

Gnomad OTH

AF:

0.276

GnomAD3 exomes

AF:

0.351

AC:

88166

AN:

251354

Hom.:

17966

AF XY:

0.353

AC XY:

47928

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.0965

Gnomad AMR exome

AF:

0.443

Gnomad ASJ exome

AF:

0.264

Gnomad EAS exome

AF:

0.740

Gnomad SAS exome

AF:

0.426

Gnomad FIN exome

AF:

0.295

Gnomad NFE exome

AF:

0.296

Gnomad OTH exome

AF:

0.318

GnomAD4 exome

AF:

0.320

AC:

463717

AN:

1447260

Hom.:

80888

Cov.:

AF XY:

0.324

AC XY:

233676

AN XY:

720904

show subpopulations

Gnomad4 AFR exome

AF:

0.0876

Gnomad4 AMR exome

AF:

0.432

Gnomad4 ASJ exome

AF:

0.263

Gnomad4 EAS exome

AF:

0.754

Gnomad4 SAS exome

AF:

0.427

Gnomad4 FIN exome

AF:

0.300

Gnomad4 NFE exome

AF:

0.301

Gnomad4 OTH exome

AF:

0.321

GnomAD4 genome

AF:

0.268

AC:

40843

AN:

152164

Hom.:

6899

Cov.:

AF XY:

0.272

AC XY:

20206

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.104

Gnomad4 AMR

AF:

0.338

Gnomad4 ASJ

AF:

0.268

Gnomad4 EAS

AF:

0.744

Gnomad4 SAS

AF:

0.423

Gnomad4 FIN

AF:

0.288

Gnomad4 NFE

AF:

0.304

Gnomad4 OTH

AF:

0.281

Alfa

AF:

0.305

Hom.:

19758

Bravo

AF:

0.266

TwinsUK

AF:

0.290

AC:

1077

ALSPAC

AF:

0.311

AC:

1197

ESP6500AA

AF:

0.112

AC:

493

ESP6500EA

AF:

0.297

AC:

2550

ExAC

AF:

0.341

AC:

41448

Asia WGS

AF:

0.504

AC:

1752

AN:

3478

EpiCase

AF:

0.295

EpiControl

AF:

0.287

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.0070

DANN

Benign

0.52

DEOGEN2

Benign

0.038

T;T

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0018

LIST_S2

Benign

0.29

T;.

MetaRNN

Benign

0.0000023

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.84

N;N

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.010

N;N

REVEL

Benign

0.0090

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.015

ClinPred

0.00030

GERP RS

-5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.031

gMVP

0.18

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over