1-109717418-A-G

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.649A>G(p.Ser217Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00931 in 1,612,738 control chromosomes in the GnomAD database, including 90 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0076 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0095 ( 81 hom. )

Consequence

GSTM5
NM_000851.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.533

Publications

12 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.0034254491).

BP6

Variant 1-109717418-A-G is Benign according to our data. Variant chr1-109717418-A-G is described in ClinVar as Benign. ClinVar VariationId is 713558.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.649A>G	p.Ser217Gly	missense	Exon 8 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.649A>G	p.Ser217Gly	missense	Exon 8 of 8	ENSP00000256593.3	P46439
GSTM5	ENST00000878690.1		c.727A>G	p.Ser243Gly	missense	Exon 9 of 9	ENSP00000548749.1
GSTM5	ENST00000966870.1		c.727A>G	p.Ser243Gly	missense	Exon 10 of 10	ENSP00000636929.1

Frequencies

GnomAD3 genomes

AF:

0.00756

AC:

1151

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00191

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00281

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.0300

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0100

Gnomad OTH

AF:

0.00382

GnomAD2 exomes

AF:

0.00814

AC:

2046

AN:

251460

AF XY:

0.00841

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.00278

Gnomad ASJ exome

AF:

0.00198

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0267

Gnomad NFE exome

AF:

0.0101

Gnomad OTH exome

AF:

0.00587

GnomAD4 exome

AF:

0.00949

AC:

13863

AN:

1460450

Hom.:

Cov.:

AF XY:

0.00943

AC XY:

6849

AN XY:

726678

show subpopulations

African (AFR)

AF:

0.00155

AC:

AN:

33442

American (AMR)

AF:

0.00288

AC:

129

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00149

AC:

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39692

South Asian (SAS)

AF:

0.00471

AC:

406

AN:

86238

European-Finnish (FIN)

AF:

0.0227

AC:

1210

AN:

53398

Middle Eastern (MID)

AF:

0.00295

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0104

AC:

11588

AN:

1110730

Other (OTH)

AF:

0.00698

AC:

421

AN:

60334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

603

1206

1809

2412

3015

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

448

896

1344

1792

2240

<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:

0.00756

AC:

1151

AN:

152288

Hom.:

Cov.:

AF XY:

0.00827

AC XY:

616

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.00190

AC:

AN:

41556

American (AMR)

AF:

0.00281

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00269

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0300

AC:

318

AN:

10612

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0100

AC:

683

AN:

68020

Other (OTH)

AF:

0.00378

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

111

167

222

278

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:

0.00818

Hom.:

Bravo

AF:

0.00538

TwinsUK

AF:

0.0113

AC:

ALSPAC

AF:

0.00908

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00779

AC:

ExAC

AF:

0.00782

AC:

949

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00834

EpiControl

AF:

0.00895

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.79

CADD

Benign

3.8

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.0041

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.42

MetaRNN

Benign

0.0034

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-0.85

PhyloP100

0.53

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.3

REVEL

Benign

0.10

Sift

Benign

0.44

Sift4G

Benign

0.45

Polyphen

0.0

Vest4

0.036

MVP

0.067

MPC

0.098

ClinPred

0.0048

GERP RS

3.1

Varity_R

0.12

gMVP

0.10

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