NM_145870.3:c.124G>A

Variant names:

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTZ1	NM_145870.3 link	c.124G>A	p.Gly42Arg	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.124G>A	p.Gly42Arg	missense_variant	Exon 3 of 9	1	NM_145870.3	ENSP00000216465.5		A0A0C4DFM0

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

GnomAD3 exomes

AF:

0.0700

AC:

16439

AN:

234830

Hom.:

955

AF XY:

0.0696

AC XY:

8819

AN XY:

126684

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 SAS exome

AF:

0.0244

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

Gnomad4 AFR exome

AF:

0.0111

Gnomad4 AMR exome

AF:

0.0313

Gnomad4 ASJ exome

AF:

0.0452

Gnomad4 EAS exome

AF:

0.000152

Gnomad4 SAS exome

AF:

0.0259

Gnomad4 FIN exome

AF:

0.212

Gnomad4 NFE exome

AF:

0.0889

Gnomad4 OTH exome

AF:

0.0735

GnomAD4 genome

AF:

0.0686

AC:

10443

AN:

152338

Hom.:

620

Cov.:

AF XY:

0.0717

AC XY:

5343

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0145

Gnomad4 AMR

AF:

0.0402

Gnomad4 ASJ

AF:

0.0507

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0222

Gnomad4 FIN

AF:

0.210

Gnomad4 NFE

AF:

0.0947

Gnomad4 OTH

AF:

0.0605

Alfa

AF:

0.0794

Hom.:

1381

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

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

- -

Sep 17, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 10739172, 25525159, 19252927) -

GSTZ1-related disorder

Benign:1

Nov 26, 2019

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

0.27

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.44

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.075

.;T;T;.;.

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.85

D;D;D;D;D

MetaRNN

Benign

0.0017

T;T;T;T;T

MetaSVM

Benign

-1.2

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-5.9

D;D;D;D;D

REVEL

Benign

0.26

Sift

Uncertain

0.0070

D;D;D;D;D

Sift4G

Uncertain

0.010

D;D;D;D;D

Vest4

0.21

MutPred

0.45

Gain of solvent accessibility (P = 0.0037);Gain of solvent accessibility (P = 0.0037);Gain of solvent accessibility (P = 0.0037);Gain of solvent accessibility (P = 0.0037);.;

MPC

0.067

ClinPred

0.026

GERP RS

5.6

gMVP

0.86

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over