Genetic Variant GSTZ1:c.67+776C>T (chr14-77325697-C-T) – 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.67+776C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,082 control chromosomes in the GnomAD database, including 2,299 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 0.14 ( 2299 hom., cov: 32)

Exomes 𝑓: 0.045 ( 0 hom. )

Consequence

GSTZ1
NM_145870.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.55

Publications

5 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:

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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).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.303 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	Effect	Exon Rank	Protein	UniProt
GSTZ1	NM_145870.3	MANE Select	c.67+776C>T	intron	N/A	NP_665877.1	A0A0C4DFM0
GSTZ1	NM_001363703.2		c.70+776C>T	intron	N/A	NP_001350632.1	G3V4T6
GSTZ1	NM_145871.3		c.67+776C>T	intron	N/A	NP_665878.2	A0A0A0MR33

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GSTZ1	ENST00000216465.10	TSL:1 MANE Select	c.67+776C>T	intron	N/A	ENSP00000216465.5	A0A0C4DFM0
GSTZ1	ENST00000361389.8	TSL:1	c.-99+776C>T	intron	N/A	ENSP00000354959.4	O43708-2
GSTZ1	ENST00000553838.5	TSL:1	n.237+776C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.139

AC:

21059

AN:

151942

Hom.:

2292

Cov.:

show subpopulations

Gnomad AFR

AF:

0.307

Gnomad AMI

AF:

0.173

Gnomad AMR

AF:

0.0729

Gnomad ASJ

AF:

0.0827

Gnomad EAS

AF:

0.00696

Gnomad SAS

AF:

0.114

Gnomad FIN

AF:

0.0741

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0758

Gnomad OTH

AF:

0.125

GnomAD4 exome

AF:

0.0455

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0455

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.139

AC:

21100

AN:

152060

Hom.:

2299

Cov.:

AF XY:

0.135

AC XY:

10074

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.307

AC:

12731

AN:

41428

American (AMR)

AF:

0.0728

AC:

1113

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0827

AC:

287

AN:

3470

East Asian (EAS)

AF:

0.00697

AC:

AN:

5162

South Asian (SAS)

AF:

0.115

AC:

555

AN:

4818

European-Finnish (FIN)

AF:

0.0741

AC:

786

AN:

10604

Middle Eastern (MID)

AF:

0.0782

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0758

AC:

5150

AN:

67968

Other (OTH)

AF:

0.124

AC:

261

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

844

1687

2531

3374

4218

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

214

428

642

856

1070

<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:

0.110

Hom.:

243

Bravo

AF:

0.144

Asia WGS

AF:

0.0810

AC:

284

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.71

(source)

DANN

Benign

0.47

PhyloP100

-1.6

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over