Genetic Variant GSTZ1:c.16-341T>A (chr14-77324529-T-A) – 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.16-341T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 1,387,252 control chromosomes in the GnomAD database, including 59,162 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 0.24 ( 5183 hom., cov: 32)

Exomes 𝑓: 0.29 ( 53979 hom. )

Consequence

GSTZ1
NM_145870.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0890

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:

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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=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTZ1	NM_145870.3 link	c.16-341T>A		intron_variant	Intron 1 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.16-341T>A		intron_variant	Intron 1 of 8	1	NM_145870.3	ENSP00000216465.5		A0A0C4DFM0

Frequencies

GnomAD3 genomes

AF:

0.237

AC:

35938

AN:

151952

Hom.:

5172

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0831

Gnomad AMI

AF:

0.295

Gnomad AMR

AF:

0.191

Gnomad ASJ

AF:

0.281

Gnomad EAS

AF:

0.436

Gnomad SAS

AF:

0.191

Gnomad FIN

AF:

0.393

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.302

Gnomad OTH

AF:

0.220

GnomAD4 exome

AF:

0.288

AC:

355542

AN:

1235184

Hom.:

53979

Cov.:

AF XY:

0.285

AC XY:

175720

AN XY:

616836

show subpopulations

African (AFR)

AF:

0.0769

AC:

2211

AN:

28770

American (AMR)

AF:

0.178

AC:

6328

AN:

35520

Ashkenazi Jewish (ASJ)

AF:

0.277

AC:

6735

AN:

24344

East Asian (EAS)

AF:

0.455

AC:

15939

AN:

35062

South Asian (SAS)

AF:

0.175

AC:

13316

AN:

76238

European-Finnish (FIN)

AF:

0.388

AC:

13101

AN:

33784

Middle Eastern (MID)

AF:

0.173

AC:

935

AN:

5396

European-Non Finnish (NFE)

AF:

0.300

AC:

282480

AN:

943048

Other (OTH)

AF:

0.273

AC:

14497

AN:

53022

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

12397

24794

37192

49589

61986

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.236

AC:

35955

AN:

152068

Hom.:

5183

Cov.:

AF XY:

0.239

AC XY:

17733

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.0831

AC:

3450

AN:

41526

American (AMR)

AF:

0.190

AC:

2909

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.281

AC:

974

AN:

3470

East Asian (EAS)

AF:

0.438

AC:

2258

AN:

5154

South Asian (SAS)

AF:

0.190

AC:

919

AN:

4828

European-Finnish (FIN)

AF:

0.393

AC:

4139

AN:

10538

Middle Eastern (MID)

AF:

0.190

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.302

AC:

20503

AN:

67952

Other (OTH)

AF:

0.227

AC:

480

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1329

2657

3986

5314

6643

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.279

Hom.:

828

Bravo

AF:

0.217

Asia WGS

AF:

0.308

AC:

1066

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

(source)

DANN

Benign

0.70

PhyloP100

0.089

PromoterAI

-0.042

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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chr14-77324529-T-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over