1-109690343-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 13/22 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

Publications

2 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 2638985.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 52 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000561.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTM1	NM_000561.4	MANE Select	c.433C>T	p.Arg145Trp	missense	Exon 6 of 8	NP_000552.2
	GSTM1	NM_146421.3		c.433C>T	p.Arg145Trp	missense	Exon 6 of 7	NP_666533.1	X5D932

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GSTM1	ENST00000309851.10	TSL:1 MANE Select	c.433C>T	p.Arg145Trp	missense	Exon 6 of 8	ENSP00000311469.5	P09488-1
GSTM1	ENST00000349334.7	TSL:1	c.433C>T	p.Arg145Trp	missense	Exon 6 of 7	ENSP00000234981.4	P09488-2
GSTM1	ENST00000369819.2	TSL:1	c.360+1018C>T		intron	N/A	ENSP00000358834.2	B9ZVX7

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

GnomAD2 exomes

AF:

0.00156

AC:

207

AN:

132336

AF XY:

0.00155

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 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

African (AFR)

AF:

0.000122

AC:

AN:

24552

American (AMR)

AF:

0.0000800

AC:

AN:

24988

Ashkenazi Jewish (ASJ)

AF:

0.0103

AC:

138

AN:

13418

East Asian (EAS)

AF:

0.00

AC:

AN:

18000

South Asian (SAS)

AF:

0.0000771

AC:

AN:

51902

European-Finnish (FIN)

AF:

0.000553

AC:

AN:

28920

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2564

European-Non Finnish (NFE)

AF:

0.00152

AC:

792

AN:

520214

Other (OTH)

AF:

0.00174

AC:

AN:

29962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00159

AC:

131

AN:

82424

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

AN XY:

40156

show subpopulations

African (AFR)

AF:

0.000172

AC:

AN:

29092

American (AMR)

AF:

0.00

AC:

AN:

7828

Ashkenazi Jewish (ASJ)

AF:

0.0163

AC:

AN:

1780

East Asian (EAS)

AF:

0.00

AC:

AN:

2220

South Asian (SAS)

AF:

0.00

AC:

AN:

2732

European-Finnish (FIN)

AF:

0.000732

AC:

AN:

5468

Middle Eastern (MID)

AF:

0.00

AC:

AN:

144

European-Non Finnish (NFE)

AF:

0.00293

AC:

AN:

31740

Other (OTH)

AF:

0.00

AC:

AN:

1076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00227

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.32

Eigen

Benign

-0.082

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.85

M_CAP

Benign

0.0048

MetaRNN

Benign

0.0077

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.7

PhyloP100

-0.099

PrimateAI

Benign

0.27

PROVEAN

Pathogenic

-5.0

REVEL

Benign

0.053

Sift

Uncertain

0.011

Sift4G

Uncertain

0.020

Polyphen

1.0

Vest4

0.19

MVP

0.53

MPC

1.2

ClinPred

0.24

GERP RS

1.4

Varity_R

0.55

gMVP

0.58

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over