Genetic Variant NM_145870.3:c.68-357G>C (chr14-77326481-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_145870.3(GSTZ1):c.68-357G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 202,754 control chromosomes in the GnomAD database, including 14,213 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.33 ( 9388 hom., cov: 33)

Exomes 𝑓: 0.41 ( 4825 hom. )

Consequence

GSTZ1
NM_145870.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0820

Publications

4 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTZ1	NM_145870.3 link	c.68-357G>C		intron_variant	Intron 2 of 8	ENST00000216465.10	NP_665877.1	O43708A0A0C4DFM0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTZ1	ENST00000216465.10 link	c.68-357G>C		intron_variant	Intron 2 of 8	1	NM_145870.3	ENSP00000216465.5		A0A0C4DFM0

Frequencies

GnomAD3 genomes

AF:

0.329

AC:

50047

AN:

151950

Hom.:

9394

Cov.:

show subpopulations

Gnomad AFR

AF:

0.131

Gnomad AMI

AF:

0.401

Gnomad AMR

AF:

0.419

Gnomad ASJ

AF:

0.409

Gnomad EAS

AF:

0.489

Gnomad SAS

AF:

0.438

Gnomad FIN

AF:

0.403

Gnomad MID

AF:

0.424

Gnomad NFE

AF:

0.392

Gnomad OTH

AF:

0.382

GnomAD4 exome

AF:

0.413

AC:

20927

AN:

50686

Hom.:

4825

Cov.:

AF XY:

0.415

AC XY:

10873

AN XY:

26192

show subpopulations

African (AFR)

AF:

0.119

AC:

297

AN:

2500

American (AMR)

AF:

0.468

AC:

1765

AN:

3772

Ashkenazi Jewish (ASJ)

AF:

0.427

AC:

780

AN:

1826

East Asian (EAS)

AF:

0.531

AC:

1948

AN:

3666

South Asian (SAS)

AF:

0.456

AC:

1544

AN:

3388

European-Finnish (FIN)

AF:

0.432

AC:

838

AN:

1938

Middle Eastern (MID)

AF:

0.440

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.410

AC:

12415

AN:

30304

Other (OTH)

AF:

0.405

AC:

1244

AN:

3074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.527

Heterozygous variant carriers

571

1142

1714

2285

2856

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

160

320

480

640

800

<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:

0.329

AC:

50053

AN:

152068

Hom.:

9388

Cov.:

AF XY:

0.336

AC XY:

24962

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.131

AC:

5442

AN:

41506

American (AMR)

AF:

0.419

AC:

6401

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.409

AC:

1420

AN:

3470

East Asian (EAS)

AF:

0.487

AC:

2515

AN:

5160

South Asian (SAS)

AF:

0.439

AC:

2111

AN:

4812

European-Finnish (FIN)

AF:

0.403

AC:

4255

AN:

10554

Middle Eastern (MID)

AF:

0.422

AC:

124

AN:

294

European-Non Finnish (NFE)

AF:

0.392

AC:

26620

AN:

67964

Other (OTH)

AF:

0.379

AC:

800

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1644

3289

4933

6578

8222

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

504

1008

1512

2016

2520

<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:

0.247

Hom.:

678

Bravo

AF:

0.325

Asia WGS

AF:

0.440

AC:

1532

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.0

(source)

DANN

Benign

0.78

PhyloP100

0.082

Mutation Taster

=100/0

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

Computational scores

Splicing

Publications

Other links and lift over