1-109689114-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_000561.4(GSTM1):c.244C>T(p.Arg82Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00011 ( 3 hom., cov: 12)

Exomes 𝑓: 0.00016 ( 48 hom. )

Consequence

GSTM1
NM_000561.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.67

Publications

1 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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.019731015).

BP6

Variant 1-109689114-C-T is Benign according to our data. Variant chr1-109689114-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3030837.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 3 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.244C>T	p.Arg82Cys	missense	Exon 4 of 8	NP_000552.2
	GSTM1	NM_146421.3		c.244C>T	p.Arg82Cys	missense	Exon 4 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.244C>T	p.Arg82Cys	missense	Exon 4 of 8	ENSP00000311469.5	P09488-1
GSTM1	ENST00000349334.7	TSL:1	c.244C>T	p.Arg82Cys	missense	Exon 4 of 7	ENSP00000234981.4	P09488-2
GSTM1	ENST00000369819.2	TSL:1	c.244C>T	p.Arg82Cys	missense	Exon 4 of 6	ENSP00000358834.2	B9ZVX7

Frequencies

GnomAD3 genomes

AF:

0.000111

AC:

AN:

81140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000680

AC:

AN:

132398

AF XY:

0.000436

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00467

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000164

AC:

117

AN:

715410

Hom.:

Cov.:

AF XY:

0.000126

AC XY:

AN XY:

357406

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24526

American (AMR)

AF:

0.00412

AC:

103

AN:

25028

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13408

East Asian (EAS)

AF:

0.00

AC:

AN:

18006

South Asian (SAS)

AF:

0.0000385

AC:

AN:

51912

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28936

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2564

European-Non Finnish (NFE)

AF:

0.0000192

AC:

AN:

521044

Other (OTH)

AF:

0.0000667

AC:

AN:

29986

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

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:

0.000111

AC:

AN:

81140

Hom.:

Cov.:

AF XY:

0.000127

AC XY:

AN XY:

39434

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28566

American (AMR)

AF:

0.00118

AC:

AN:

7638

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1764

East Asian (EAS)

AF:

0.00

AC:

AN:

2148

South Asian (SAS)

AF:

0.00

AC:

AN:

2664

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5370

Middle Eastern (MID)

AF:

0.00

AC:

AN:

142

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

31472

Other (OTH)

AF:

0.00

AC:

AN:

1040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.000253

Hom.:

ExAC

AF:

0.000618

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

GSTM1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.037

MetaRNN

Benign

0.020

MetaSVM

Benign

-0.85

MutationAssessor

Pathogenic

4.8

PhyloP100

2.7

PrimateAI

Uncertain

0.63

PROVEAN

Pathogenic

-7.6

REVEL

Uncertain

0.36

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.42

MutPred

0.69

Loss of catalytic residue at R82 (P = 0.0433)

MVP

0.35

MPC

2.4

ClinPred

0.41

GERP RS

3.3

Varity_R

0.96

gMVP

0.56

Mutation Taster

=94/6

polymorphism

(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