rs8177544

Variant names:

• chr14-77322445-C-T
• rs8177544
• NM_145870.3:c.15+1262C>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.15+1262C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0566 in 229,798 control chromosomes in the GnomAD database, including 609 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 0.064 (530 hom., cov: 32)
  • Exomes 𝑓: 0.042 (79 hom.)
• Consequence: GSTZ1 NM_145870.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.859
• Publications: 3 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.135 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTZ1	NM_145870.3	MANE Select	c.15+1262C>T		intron	N/A	NP_665877.1
	GSTZ1	NM_145871.3		c.15+1262C>T		intron	N/A	NP_665878.2
	GSTZ1	NM_001312660.2		c.-336-102C>T		intron	N/A	NP_001299589.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTZ1	ENST00000216465.10	TSL:1 MANE Select	c.15+1262C>T		intron	N/A	ENSP00000216465.5
	GSTZ1	ENST00000361389.8	TSL:1	c.-336-102C>T		intron	N/A	ENSP00000354959.4
	GSTZ1	ENST00000553838.5	TSL:1	n.185+1262C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0639 AC: 9715 AN: 152092 Hom.: 530 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0296

Gnomad ASJ AF: 0.0239

Gnomad EAS AF: 0.00655

Gnomad SAS AF: 0.0877

Gnomad FIN AF: 0.0225

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0378

Gnomad OTH AF: 0.0517

GnomAD4 exome AF: 0.0423 AC: 3282 AN: 77588 Hom.: 79 AF XY: 0.0425 AC XY: 1599 AN XY: 37634

African (AFR) AF: 0.146 AC: 207 AN: 1422

American (AMR) AF: 0.0139 AC: 1 AN: 72

Ashkenazi Jewish (ASJ) AF: 0.0286 AC: 14 AN: 490

East Asian (EAS) AF: 0.00704 AC: 2 AN: 284

South Asian (SAS) AF: 0.0965 AC: 155 AN: 1606

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36

Middle Eastern (MID) AF: 0.0270 AC: 4 AN: 148

European-Non Finnish (NFE) AF: 0.0389 AC: 2760 AN: 70920

Other (OTH) AF: 0.0533 AC: 139 AN: 2610

GnomAD4 genome AF: 0.0639 AC: 9724 AN: 152210 Hom.: 530 Cov.: 32 AF XY: 0.0629 AC XY: 4683 AN XY: 74426

African (AFR) AF: 0.138 AC: 5719 AN: 41492

American (AMR) AF: 0.0295 AC: 452 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0239 AC: 83 AN: 3470

East Asian (EAS) AF: 0.00656 AC: 34 AN: 5182

South Asian (SAS) AF: 0.0880 AC: 425 AN: 4828

European-Finnish (FIN) AF: 0.0225 AC: 239 AN: 10610

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0377 AC: 2565 AN: 68014

Other (OTH) AF: 0.0512 AC: 108 AN: 2110

Alfa AF: 0.0416 Hom.: 238

Bravo AF: 0.0652

Asia WGS AF: 0.0540 AC: 189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.5
DANN	Benign	0.69
PhyloP100		0.86
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: rs8177544; hg19: chr14-77788788;