dbSNP rs8177565: GSTZ1:c.342+517G>A (chr14-77328554-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_145870.3(GSTZ1):c.342+517G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0182 in 172,398 control chromosomes in the GnomAD database, including 53 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 0.018 ( 45 hom., cov: 33)

Exomes 𝑓: 0.020 ( 8 hom. )

Consequence

GSTZ1
NM_145870.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.362

Publications

3 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=-0.82).

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.018 (2739/152328) while in subpopulation SAS AF = 0.0413 (199/4824). AF 95% confidence interval is 0.0366. There are 45 homozygotes in GnomAd4. There are 1346 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 45 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTZ1	NM_145870.3 link	c.342+517G>A		intron_variant	Intron 5 of 8	ENST00000216465.10	NP_665877.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTZ1	ENST00000216465.10 link	c.342+517G>A		intron_variant	Intron 5 of 8	1	NM_145870.3	ENSP00000216465.5

Frequencies

GnomAD3 genomes

AF:

0.0180

AC:

2746

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00453

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0186

Gnomad ASJ

AF:

0.0573

Gnomad EAS

AF:

0.0189

Gnomad SAS

AF:

0.0418

Gnomad FIN

AF:

0.0155

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0224

Gnomad OTH

AF:

0.0315

GnomAD4 exome

AF:

0.0201

AC:

404

AN:

20070

Hom.:

Cov.:

AF XY:

0.0219

AC XY:

221

AN XY:

10106

show subpopulations

African (AFR)

AF:

0.00296

AC:

AN:

338

American (AMR)

AF:

0.0261

AC:

AN:

2376

Ashkenazi Jewish (ASJ)

AF:

0.0385

AC:

AN:

364

East Asian (EAS)

AF:

0.00458

AC:

AN:

874

South Asian (SAS)

AF:

0.0335

AC:

AN:

1850

European-Finnish (FIN)

AF:

0.00923

AC:

AN:

542

Middle Eastern (MID)

AF:

0.0625

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0181

AC:

228

AN:

12612

Other (OTH)

AF:

0.0222

AC:

AN:

1034

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

112

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0180

AC:

2739

AN:

152328

Hom.:

Cov.:

AF XY:

0.0181

AC XY:

1346

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.00450

AC:

187

AN:

41578

American (AMR)

AF:

0.0185

AC:

283

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0573

AC:

199

AN:

3472

East Asian (EAS)

AF:

0.0187

AC:

AN:

5186

South Asian (SAS)

AF:

0.0413

AC:

199

AN:

4824

European-Finnish (FIN)

AF:

0.0155

AC:

165

AN:

10620

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0224

AC:

1521

AN:

68028

Other (OTH)

AF:

0.0307

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

141

282

422

563

704

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.0199

Hom.:

Bravo

AF:

0.0166

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.67

(source)

DANN

Benign

0.63

PhyloP100

-0.36

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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