rs7975

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.94G>A(p.Glu32Lys) variant causes a missense change. The variant allele was found at a frequency of 0.32 in 1,602,590 control chromosomes in the GnomAD database, including 83,900 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 7778 hom., cov: 33)

Exomes 𝑓: 0.32 ( 76122 hom. )

Consequence

GSTZ1
NM_145870.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 5.23

Publications

72 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=0.0017864704).

BP6

Variant 14-77326864-G-A is Benign according to our data. Variant chr14-77326864-G-A is described in ClinVar as Benign. ClinVar VariationId is 1251643.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTZ1	NM_145870.3 link	c.94G>A	p.Glu32Lys	missense_variant	Exon 3 of 9	ENST00000216465.10	NP_665877.1	O43708A0A0C4DFM0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTZ1	ENST00000216465.10 link	c.94G>A	p.Glu32Lys	missense_variant	Exon 3 of 9	1	NM_145870.3	ENSP00000216465.5		A0A0C4DFM0

Frequencies

GnomAD3 genomes

AF:

0.316

AC:

48040

AN:

152028

Hom.:

7764

Cov.:

show subpopulations

Gnomad AFR

AF:

0.298

Gnomad AMI

AF:

0.299

Gnomad AMR

AF:

0.231

Gnomad ASJ

AF:

0.340

Gnomad EAS

AF:

0.457

Gnomad SAS

AF:

0.236

Gnomad FIN

AF:

0.393

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.328

Gnomad OTH

AF:

0.295

GnomAD2 exomes

AF:

0.307

AC:

73131

AN:

238540

AF XY:

0.304

show subpopulations

Gnomad AFR exome

AF:

0.297

Gnomad AMR exome

AF:

0.204

Gnomad ASJ exome

AF:

0.326

Gnomad EAS exome

AF:

0.452

Gnomad FIN exome

AF:

0.388

Gnomad NFE exome

AF:

0.323

Gnomad OTH exome

AF:

0.315

GnomAD4 exome

AF:

0.320

AC:

464016

AN:

1450444

Hom.:

76122

Cov.:

AF XY:

0.317

AC XY:

228578

AN XY:

720864

show subpopulations

African (AFR)

AF:

0.295

AC:

9839

AN:

33358

American (AMR)

AF:

0.206

AC:

9012

AN:

43832

Ashkenazi Jewish (ASJ)

AF:

0.334

AC:

8642

AN:

25906

East Asian (EAS)

AF:

0.489

AC:

19327

AN:

39560

South Asian (SAS)

AF:

0.219

AC:

18528

AN:

84790

European-Finnish (FIN)

AF:

0.390

AC:

20623

AN:

52830

Middle Eastern (MID)

AF:

0.245

AC:

1410

AN:

5750

European-Non Finnish (NFE)

AF:

0.324

AC:

357515

AN:

1104438

Other (OTH)

AF:

0.319

AC:

19120

AN:

59980

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

14277

28555

42832

57110

71387

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11590

23180

34770

46360

57950

<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:

0.316

AC:

48070

AN:

152146

Hom.:

7778

Cov.:

AF XY:

0.315

AC XY:

23435

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.298

AC:

12378

AN:

41502

American (AMR)

AF:

0.231

AC:

3525

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.340

AC:

1181

AN:

3472

East Asian (EAS)

AF:

0.459

AC:

2374

AN:

5170

South Asian (SAS)

AF:

0.234

AC:

1128

AN:

4818

European-Finnish (FIN)

AF:

0.393

AC:

4163

AN:

10584

Middle Eastern (MID)

AF:

0.272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.328

AC:

22333

AN:

67992

Other (OTH)

AF:

0.301

AC:

635

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1719

3438

5157

6876

8595

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

486

972

1458

1944

2430

<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:

0.312

Hom.:

23811

Bravo

AF:

0.304

TwinsUK

AF:

0.332

AC:

1231

ALSPAC

AF:

0.322

AC:

1242

ESP6500AA

AF:

0.295

AC:

1299

ESP6500EA

AF:

0.327

AC:

2814

ExAC

AF:

0.300

AC:

36415

Asia WGS

AF:

0.345

AC:

1195

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 13, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 22374552) -

GSTZ1-related disorder

Benign:1

Mar 16, 2020

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.44

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.082

.;T;T;.;.

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.83

T;D;D;D;T

MetaRNN

Benign

0.0018

T;T;T;T;T

MetaSVM

Benign

-0.90

PhyloP100

5.2

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-3.3

D;D;D;D;D

REVEL

Benign

0.27

Sift

Uncertain

0.027

D;D;D;D;D

Sift4G

Benign

0.092

T;T;T;T;T

Vest4

0.22

MPC

0.059

ClinPred

0.017

GERP RS

5.6

gMVP

0.70

Mutation Taster

=154/146

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over