1-109715232-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_000851.4(GSTM5):c.559C>T(p.Arg187Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0069 in 1,614,192 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0055 ( 9 hom., cov: 33)

Exomes 𝑓: 0.0070 ( 54 hom. )

Consequence

GSTM5
NM_000851.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.95

Publications

14 publications found

Variant links:

Genes affected

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011373311).

BP6

Variant 1-109715232-C-T is Benign according to our data. Variant chr1-109715232-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 708302.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000851.4. 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
	GSTM5	NM_000851.4	MANE Select	c.559C>T	p.Arg187Cys	missense	Exon 7 of 8	NP_000842.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GSTM5	ENST00000256593.8	TSL:1 MANE Select	c.559C>T	p.Arg187Cys	missense	Exon 7 of 8	ENSP00000256593.3	P46439
GSTM5	ENST00000878690.1		c.637C>T	p.Arg213Cys	missense	Exon 8 of 9	ENSP00000548749.1
GSTM5	ENST00000966870.1		c.637C>T	p.Arg213Cys	missense	Exon 9 of 10	ENSP00000636929.1

Frequencies

GnomAD3 genomes

AF:

0.00548

AC:

834

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.00596

Gnomad ASJ

AF:

0.00923

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00883

Gnomad OTH

AF:

0.00860

GnomAD2 exomes

AF:

0.00560

AC:

1409

AN:

251496

AF XY:

0.00566

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.00494

Gnomad ASJ exome

AF:

0.0122

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000739

Gnomad NFE exome

AF:

0.00868

Gnomad OTH exome

AF:

0.00863

GnomAD4 exome

AF:

0.00705

AC:

10301

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00686

AC XY:

4992

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.000956

AC:

AN:

33478

American (AMR)

AF:

0.00521

AC:

233

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0115

AC:

300

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000916

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000768

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.0151

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00815

AC:

9059

AN:

1112008

Other (OTH)

AF:

0.00778

AC:

470

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

673

1346

2018

2691

3364

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

326

652

978

1304

1630

<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:

0.00548

AC:

834

AN:

152304

Hom.:

Cov.:

AF XY:

0.00491

AC XY:

366

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.00135

AC:

AN:

41560

American (AMR)

AF:

0.00595

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00923

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000829

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000471

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00883

AC:

601

AN:

68026

Other (OTH)

AF:

0.00851

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

121

161

201

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00740

Hom.:

Bravo

AF:

0.00596

TwinsUK

AF:

0.00701

AC:

ALSPAC

AF:

0.00830

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00977

AC:

ExAC

AF:

0.00553

AC:

671

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00927

EpiControl

AF:

0.0113

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.93

M_CAP

Pathogenic

0.29

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.92

MutationAssessor

Pathogenic

4.0

PhyloP100

2.9

PrimateAI

Benign

0.33

PROVEAN

Pathogenic

-5.8

REVEL

Benign

0.22

Sift

Benign

0.042

Sift4G

Uncertain

0.023

Polyphen

0.73

Vest4

0.76

MVP

0.29

MPC

0.47

ClinPred

0.11

GERP RS

5.0

Varity_R

0.40

gMVP

0.36

Mutation Taster

=98/2

polymorphism

(source)

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

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