rs8004558

Variant names:

• chr14-77325697-C-T
• rs8004558
• NM_145870.3:c.67+776C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55
• Publications: 5 publications found

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

ACMG classification

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTZ1	NM_145870.3	c.67+776C>T		intron_variant	Intron 2 of 8	ENST00000216465.10	NP_665877.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTZ1	ENST00000216465.10	c.67+776C>T		intron_variant	Intron 2 of 8	1	NM_145870.3	ENSP00000216465.5

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21059 AN: 151942 Hom.: 2292 Cov.: 32

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: 1 AN: 22 Hom.: 0 Cov.: 0 AF XY: 0.0455 AC XY: 1 AN XY: 22

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 16

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.139 AC: 21100 AN: 152060 Hom.: 2299 Cov.: 32 AF XY: 0.135 AC XY: 10074 AN XY: 74354

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: 36 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: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0758 AC: 5150 AN: 67968

Other (OTH) AF: 0.124 AC: 261 AN: 2112

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.71
DANN	Benign	0.47
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8004558; hg19: chr14-77792040;