rs8177573

Variant names:

• chr14-77330415-C-T
• rs8177573
• NM_145870.3:c.524+56C>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.524+56C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0461 in 1,393,758 control chromosomes in the GnomAD database, including 1,756 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 0.039 (151 hom., cov: 32)
  • Exomes 𝑓: 0.047 (1605 hom.)
• Consequence: GSTZ1 NM_145870.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0567 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTZ1	NM_145870.3	MANE Select	c.524+56C>T		intron	N/A	NP_665877.1	A0A0C4DFM0
	GSTZ1	NM_001363703.2		c.527+56C>T		intron	N/A	NP_001350632.1	G3V4T6
	GSTZ1	NM_145871.3		c.398+56C>T		intron	N/A	NP_665878.2	A0A0A0MR33

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTZ1	ENST00000216465.10	TSL:1 MANE Select	c.524+56C>T		intron	N/A	ENSP00000216465.5	A0A0C4DFM0
	GSTZ1	ENST00000361389.8	TSL:1	c.359+56C>T		intron	N/A	ENSP00000354959.4	O43708-2
	GSTZ1	ENST00000553586.5	TSL:5	c.527+56C>T		intron	N/A	ENSP00000451976.1	G3V4T6

Frequencies

GnomAD3 genomes AF: 0.0386 AC: 5876 AN: 152184 Hom.: 151 Cov.: 32

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.00879

Gnomad AMR AF: 0.0373

Gnomad ASJ AF: 0.0554

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0141

Gnomad FIN AF: 0.0512

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0582

Gnomad OTH AF: 0.0407

GnomAD4 exome AF: 0.0470 AC: 58334 AN: 1241456 Hom.: 1605 AF XY: 0.0463 AC XY: 29071 AN XY: 628360

African (AFR) AF: 0.00924 AC: 267 AN: 28910

American (AMR) AF: 0.0293 AC: 1302 AN: 44454

Ashkenazi Jewish (ASJ) AF: 0.0507 AC: 1258 AN: 24790

East Asian (EAS) AF: 0.000103 AC: 4 AN: 38762

South Asian (SAS) AF: 0.0114 AC: 930 AN: 81932

European-Finnish (FIN) AF: 0.0455 AC: 2425 AN: 53284

Middle Eastern (MID) AF: 0.0477 AC: 250 AN: 5244

European-Non Finnish (NFE) AF: 0.0545 AC: 49612 AN: 911028

Other (OTH) AF: 0.0431 AC: 2286 AN: 53052

GnomAD4 genome AF: 0.0386 AC: 5872 AN: 152302 Hom.: 151 Cov.: 32 AF XY: 0.0369 AC XY: 2750 AN XY: 74472

African (AFR) AF: 0.0104 AC: 432 AN: 41584

American (AMR) AF: 0.0371 AC: 568 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0554 AC: 192 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.0137 AC: 66 AN: 4822

European-Finnish (FIN) AF: 0.0512 AC: 544 AN: 10622

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0582 AC: 3957 AN: 68016

Other (OTH) AF: 0.0408 AC: 86 AN: 2108

Alfa AF: 0.0474 Hom.: 74

Bravo AF: 0.0369

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.35
DANN	Benign	0.52
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs8177573; hg19: chr14-77796758;