Variant 14-77326864-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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=0.0017864704).

BP6

Variant 14-77326864-G-A is Benign according to our data. Variant chr14-77326864-G-A is described in ClinVar as [Benign]. Clinvar id 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/exons	MANE	UniProt
GSTZ1	NM_145870.3 linkuse as main transcript	c.94G>A	p.Glu32Lys	missense_variant	3/9	ENST00000216465.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTZ1	ENST00000216465.10 linkuse as main transcript	c.94G>A	p.Glu32Lys	missense_variant	3/9	1	NM_145870.3

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

GnomAD3 exomes

AF:

0.307

AC:

73131

AN:

238540

Hom.:

11752

AF XY:

0.304

AC XY:

39187

AN XY:

128836

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 SAS exome

AF:

0.214

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

Gnomad4 AFR exome

AF:

0.295

Gnomad4 AMR exome

AF:

0.206

Gnomad4 ASJ exome

AF:

0.334

Gnomad4 EAS exome

AF:

0.489

Gnomad4 SAS exome

AF:

0.219

Gnomad4 FIN exome

AF:

0.390

Gnomad4 NFE exome

AF:

0.324

Gnomad4 OTH exome

AF:

0.319

GnomAD4 genome

AF:

0.316

AC:

48070

AN:

152146

Hom.:

7778

Cov.:

AF XY:

0.315

AC XY:

23435

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.298

Gnomad4 AMR

AF:

0.231

Gnomad4 ASJ

AF:

0.340

Gnomad4 EAS

AF:

0.459

Gnomad4 SAS

AF:

0.234

Gnomad4 FIN

AF:

0.393

Gnomad4 NFE

AF:

0.328

Gnomad4 OTH

AF:

0.301

Alfa

AF:

0.323

Hom.:

15067

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 13, 2019	This variant is associated with the following publications: (PMID: 22374552) -

GSTZ1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 16, 2020

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

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

MutationTaster

Benign

2.1e-7

P;P;P;P;P;P;P;P;P

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

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

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