chr1-109690343-C-T

Position:

chr1-109690343-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000561.4(GSTM1):c.433C>T(p.Arg145Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 52 hom., cov: 13)

Exomes 𝑓: 0.0014 ( 426 hom. )

Consequence

GSTM1
NM_000561.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0990

Variant links:

Genes affected

GSTM1 (HGNC:4632): (glutathione S-transferase mu 1) 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. Null mutations of this class mu gene have been linked with an increase in a number of cancers, likely due to an increased susceptibility to environmental toxins and carcinogens. Multiple protein isoforms are encoded by transcript variants of this gene. [provided by RefSeq, Jul 2008]

GSTM1 links:

GSTM2 (HGNC:4634): (glutathione S-transferase mu 2) 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. [provided by RefSeq, Jul 2008]

GSTM2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007727623).

BP6

Variant 1-109690343-C-T is Benign according to our data. Variant chr1-109690343-C-T is described in ClinVar as [Benign]. Clinvar id is 2638985.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 52 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GSTM1	NM_000561.4 linkuse as main transcript	c.433C>T	p.Arg145Trp	missense_variant	6/8	ENST00000309851.10
GSTM1	NM_146421.3 linkuse as main transcript	c.433C>T	p.Arg145Trp	missense_variant	6/7
GSTM1	XM_005270782.6 linkuse as main transcript	c.331C>T	p.Arg111Trp	missense_variant	6/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTM1	ENST00000309851.10 linkuse as main transcript	c.433C>T	p.Arg145Trp	missense_variant	6/8	1	NM_000561.4	P1	P09488-1

Frequencies

GnomAD3 genomes

AF:

0.00159

AC:

131

AN:

82424

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000172

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.0163

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000732

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00293

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00156

AC:

207

AN:

132336

Hom.:

AF XY:

0.00155

AC XY:

110

AN XY:

71022

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0127

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000107

Gnomad FIN exome

AF:

0.000510

Gnomad NFE exome

AF:

0.00235

Gnomad OTH exome

AF:

0.00192

GnomAD4 exome

AF:

0.00141

AC:

1007

AN:

714520

Hom.:

426

Cov.:

AF XY:

0.00146

AC XY:

522

AN XY:

356980

show subpopulations

Gnomad4 AFR exome

AF:

0.000122

Gnomad4 AMR exome

AF:

0.0000800

Gnomad4 ASJ exome

AF:

0.0103

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000771

Gnomad4 FIN exome

AF:

0.000553

Gnomad4 NFE exome

AF:

0.00152

Gnomad4 OTH exome

AF:

0.00174

GnomAD4 genome

AF:

0.00159

AC:

131

AN:

82424

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

AN XY:

40156

show subpopulations

Gnomad4 AFR

AF:

0.000172

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.0163

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000732

Gnomad4 NFE

AF:

0.00293

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000933

Hom.:

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00211

AC:

ExAC

AF:

0.00125

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

GSTM1: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.32

T;T;.

Eigen

Benign

-0.082

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.85

T;T;T

M_CAP

Benign

0.0048

MetaRNN

Benign

0.0077

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.7

H;.;H

MutationTaster

Benign

1.0

N;N;N;N;N;N;N

PrimateAI

Benign

0.27

PROVEAN

Pathogenic

-5.0

D;D;D

REVEL

Benign

0.053

Sift

Uncertain

0.011

D;D;D

Sift4G

Uncertain

0.020

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.19

MVP

0.53

MPC

1.2

ClinPred

0.24

GERP RS

1.4

Varity_R

0.55

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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