rs7972

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_145870.3(GSTZ1):c.124G>A(p.Gly42Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0808 in 1,600,028 control chromosomes in the GnomAD database, including 6,542 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.069 ( 620 hom., cov: 33)

Exomes 𝑓: 0.082 ( 5922 hom. )

Consequence

GSTZ1
NM_145870.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 5.22

Publications

53 publications found

Variant links:

Genes affected

GSTZ1 (HGNC:4643): (glutathione S-transferase zeta 1) This gene is a member of the glutathione S-transferase (GSTs) super-family which encodes multifunctional enzymes important in the detoxification of electrophilic molecules, including carcinogens, mutagens, and several therapeutic drugs, by conjugation with glutathione. This enzyme catalyzes the conversion of maleylacetoacetate to fumarylacetoacatate, which is one of the steps in the phenylalanine/tyrosine degradation pathway. Deficiency of a similar gene in mouse causes oxidative stress. Several transcript variants of this gene encode multiple protein isoforms. [provided by RefSeq, Jul 2015]

GSTZ1 Gene-Disease associations (from GenCC):

maleylacetoacetate isomerase deficiency
Inheritance: AR Classification: MODERATE Submitted by: ClinGen

GSTZ1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016635954).

BP6

Variant 14-77326894-G-A is Benign according to our data. Variant chr14-77326894-G-A is described in ClinVar as Benign. ClinVar VariationId is 1234080.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0928 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145870.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GSTZ1	NM_145870.3	MANE Select	c.124G>A	p.Gly42Arg	missense	Exon 3 of 9	NP_665877.1	A0A0C4DFM0
GSTZ1	NM_001363703.2		c.127G>A	p.Gly43Arg	missense	Exon 3 of 9	NP_001350632.1	G3V4T6
GSTZ1	NM_145871.3		c.124G>A	p.Gly42Arg	missense	Exon 3 of 8	NP_665878.2	A0A0A0MR33

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GSTZ1	ENST00000216465.10	TSL:1 MANE Select	c.124G>A	p.Gly42Arg	missense	Exon 3 of 9	ENSP00000216465.5	A0A0C4DFM0
GSTZ1	ENST00000361389.8	TSL:1	c.-42G>A		5_prime_UTR	Exon 4 of 10	ENSP00000354959.4	O43708-2
GSTZ1	ENST00000553838.5	TSL:1	n.294G>A		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes

AF:

0.0686

AC:

10446

AN:

152220

Hom.:

620

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0145

Gnomad AMI

AF:

0.145

Gnomad AMR

AF:

0.0402

Gnomad ASJ

AF:

0.0507

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0223

Gnomad FIN

AF:

0.210

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0947

Gnomad OTH

AF:

0.0612

GnomAD2 exomes

AF:

0.0700

AC:

16439

AN:

234830

AF XY:

0.0696

show subpopulations

Gnomad AFR exome

AF:

0.0122

Gnomad AMR exome

AF:

0.0300

Gnomad ASJ exome

AF:

0.0440

Gnomad EAS exome

AF:

0.0000562

Gnomad FIN exome

AF:

0.213

Gnomad NFE exome

AF:

0.0893

Gnomad OTH exome

AF:

0.0775

GnomAD4 exome

AF:

0.0821

AC:

118870

AN:

1447690

Hom.:

5922

Cov.:

AF XY:

0.0807

AC XY:

58040

AN XY:

719280

show subpopulations

African (AFR)

AF:

0.0111

AC:

369

AN:

33346

American (AMR)

AF:

0.0313

AC:

1370

AN:

43708

Ashkenazi Jewish (ASJ)

AF:

0.0452

AC:

1168

AN:

25868

East Asian (EAS)

AF:

0.000152

AC:

AN:

39550

South Asian (SAS)

AF:

0.0259

AC:

2189

AN:

84366

European-Finnish (FIN)

AF:

0.212

AC:

11170

AN:

52700

Middle Eastern (MID)

AF:

0.0319

AC:

183

AN:

5742

European-Non Finnish (NFE)

AF:

0.0889

AC:

98012

AN:

1102470

Other (OTH)

AF:

0.0735

AC:

4403

AN:

59940

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

Heterozygous variant carriers

4703

9405

14108

18810

23513

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3396

6792

10188

13584

16980

<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:

0.0686

AC:

10443

AN:

152338

Hom.:

620

Cov.:

AF XY:

0.0717

AC XY:

5343

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0145

AC:

603

AN:

41590

American (AMR)

AF:

0.0402

AC:

615

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0507

AC:

176

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.0222

AC:

107

AN:

4830

European-Finnish (FIN)

AF:

0.210

AC:

2232

AN:

10614

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0947

AC:

6442

AN:

68024

Other (OTH)

AF:

0.0605

AC:

128

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

503

1007

1510

2014

2517

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

118

236

354

472

590

<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:

0.0777

Hom.:

2670

Bravo

AF:

0.0531

TwinsUK

AF:

0.0965

AC:

358

ALSPAC

AF:

0.0908

AC:

350

ESP6500AA

AF:

0.0177

AC:

ESP6500EA

AF:

0.0822

AC:

707

ExAC

AF:

0.0657

AC:

7970

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

GSTZ1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.44

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.075

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.85

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.2

PhyloP100

5.2

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-5.9

REVEL

Benign

0.26

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.010

Vest4

0.21

MutPred

0.45

Gain of solvent accessibility (P = 0.0037)

MPC

0.067

ClinPred

0.026

GERP RS

5.6

gMVP

0.86

Mutation Taster

=273/27

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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