rs8177569

Positions:

• chr14-77329325-A-C
• chr14-77329325-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145870.3(GSTZ1):​c.421+124A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0417 in 731,860 control chromosomes in the GnomAD database, including 841 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 0.055 (285 hom., cov: 33)
  • Exomes 𝑓: 0.038 (556 hom.)
• Consequence: GSTZ1 NM_145870.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.625

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.097 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSTZ1	NM_145870.3	c.421+124A>C		intron_variant		ENST00000216465.10	NP_665877.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSTZ1	ENST00000216465.10	c.421+124A>C		intron_variant		1	NM_145870.3	ENSP00000216465.5

Frequencies

GnomAD3 genomes AF: 0.0545 AC: 8290 AN: 152142 Hom.: 287 Cov.: 33

Gnomad AFR AF: 0.0995

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0350

Gnomad ASJ AF: 0.0550

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0258

Gnomad FIN AF: 0.0516

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0378

Gnomad OTH AF: 0.0559

GnomAD4 exome AF: 0.0383 AC: 22193 AN: 579600 Hom.: 556 Cov.: 6 AF XY: 0.0378 AC XY: 11702 AN XY: 309908

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.0242

Gnomad4 ASJ exome AF: 0.0512

Gnomad4 EAS exome AF: 0.000183

Gnomad4 SAS exome AF: 0.0283

Gnomad4 FIN exome AF: 0.0495

Gnomad4 NFE exome AF: 0.0395

Gnomad4 OTH exome AF: 0.0415

GnomAD4 genome AF: 0.0545 AC: 8301 AN: 152260 Hom.: 285 Cov.: 33 AF XY: 0.0537 AC XY: 3997 AN XY: 74472

Gnomad4 AFR AF: 0.0995

Gnomad4 AMR AF: 0.0350

Gnomad4 ASJ AF: 0.0550

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0259

Gnomad4 FIN AF: 0.0516

Gnomad4 NFE AF: 0.0378

Gnomad4 OTH AF: 0.0553

Alfa AF: 0.0421 Hom.: 129

Bravo AF: 0.0555

Asia WGS AF: 0.0220 AC: 76 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	12
DANN	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs8177569; hg19: chr14-77795668;