rs1046428

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_145870.3(GSTZ1):c.245T>C(p.Met82Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.804 in 1,613,244 control chromosomes in the GnomAD database, including 523,055 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M82I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.83 ( 52981 hom., cov: 30)

Exomes 𝑓: 0.80 ( 470074 hom. )

Consequence

GSTZ1
NM_145870.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 2.44

Publications

71 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

new If you want to explore the variant's impact on the transcript NM_145870.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.2019495E-7).

BP6

Variant 14-77327940-T-C is Benign according to our data. Variant chr14-77327940-T-C is described in ClinVar as Benign. ClinVar VariationId is 2663453.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.931 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.245T>C	p.Met82Thr	missense	Exon 5 of 9	NP_665877.1	A0A0C4DFM0
GSTZ1	NM_001363703.2		c.248T>C	p.Met83Thr	missense	Exon 5 of 9	NP_001350632.1	G3V4T6
GSTZ1	NM_001312660.2		c.80T>C	p.Met27Thr	missense	Exon 6 of 10	NP_001299589.1	O43708-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GSTZ1	ENST00000216465.10	TSL:1 MANE Select	c.245T>C	p.Met82Thr	missense	Exon 5 of 9	ENSP00000216465.5	A0A0C4DFM0
GSTZ1	ENST00000361389.8	TSL:1	c.80T>C	p.Met27Thr	missense	Exon 6 of 10	ENSP00000354959.4	O43708-2
GSTZ1	ENST00000553838.5	TSL:1	n.774T>C		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes

AF:

0.833

AC:

126469

AN:

151892

Hom.:

52937

Cov.:

show subpopulations

Gnomad AFR

AF:

0.901

Gnomad AMI

AF:

0.876

Gnomad AMR

AF:

0.744

Gnomad ASJ

AF:

0.831

Gnomad EAS

AF:

0.953

Gnomad SAS

AF:

0.792

Gnomad FIN

AF:

0.871

Gnomad MID

AF:

0.791

Gnomad NFE

AF:

0.798

Gnomad OTH

AF:

0.833

GnomAD2 exomes

AF:

0.813

AC:

204080

AN:

251120

AF XY:

0.810

show subpopulations

Gnomad AFR exome

AF:

0.907

Gnomad AMR exome

AF:

0.722

Gnomad ASJ exome

AF:

0.822

Gnomad EAS exome

AF:

0.963

Gnomad FIN exome

AF:

0.854

Gnomad NFE exome

AF:

0.802

Gnomad OTH exome

AF:

0.807

GnomAD4 exome

AF:

0.801

AC:

1170336

AN:

1461234

Hom.:

470074

Cov.:

AF XY:

0.801

AC XY:

582033

AN XY:

726960

show subpopulations

African (AFR)

AF:

0.912

AC:

30519

AN:

33476

American (AMR)

AF:

0.733

AC:

32752

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.822

AC:

21482

AN:

26134

East Asian (EAS)

AF:

0.966

AC:

38368

AN:

39698

South Asian (SAS)

AF:

0.781

AC:

67380

AN:

86246

European-Finnish (FIN)

AF:

0.853

AC:

45506

AN:

53364

Middle Eastern (MID)

AF:

0.787

AC:

4537

AN:

5768

European-Non Finnish (NFE)

AF:

0.792

AC:

880704

AN:

1111468

Other (OTH)

AF:

0.813

AC:

49088

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

11840

23680

35520

47360

59200

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20698

41396

62094

82792

103490

<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:

0.833

AC:

126569

AN:

152010

Hom.:

52981

Cov.:

AF XY:

0.834

AC XY:

61994

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.901

AC:

37365

AN:

41454

American (AMR)

AF:

0.743

AC:

11348

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.831

AC:

2886

AN:

3472

East Asian (EAS)

AF:

0.954

AC:

4898

AN:

5136

South Asian (SAS)

AF:

0.792

AC:

3817

AN:

4822

European-Finnish (FIN)

AF:

0.871

AC:

9220

AN:

10586

Middle Eastern (MID)

AF:

0.789

AC:

232

AN:

294

European-Non Finnish (NFE)

AF:

0.798

AC:

54243

AN:

67954

Other (OTH)

AF:

0.835

AC:

1761

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1084

2169

3253

4338

5422

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

882

1764

2646

3528

4410

<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:

0.810

Hom.:

242836

Bravo

AF:

0.828

Asia WGS

AF:

0.879

AC:

3060

AN:

3478

EpiCase

AF:

0.793

EpiControl

AF:

0.794

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

GSTZ1-related disorder (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.56

DEOGEN2

Benign

0.0026

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.49

MetaRNN

Benign

6.2e-7

MetaSVM

Benign

-0.97

PhyloP100

2.4

PrimateAI

Uncertain

0.60

PROVEAN

Benign

4.2

REVEL

Benign

0.090

Sift

Benign

1.0

Sift4G

Benign

1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.70

Mutation Taster

=95/5

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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