rs8177565

Positions:

• chr14-77328554-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_145870.3(GSTZ1):​c.342+517G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0182 in 172,398 control chromosomes in the GnomAD database, including 53 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 0.018 (45 hom., cov: 33)
  • Exomes 𝑓: 0.020 (8 hom.)
• Consequence: GSTZ1 NM_145870.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.362

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.018 (2739/152328) while in subpopulation SAS AF= 0.0413 (199/4824). AF 95% confidence interval is 0.0366. There are 45 homozygotes in gnomad4. There are 1346 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 45 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSTZ1	NM_145870.3	c.342+517G>A		intron_variant		ENST00000216465.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTZ1	ENST00000216465.10	c.342+517G>A		intron_variant		1	NM_145870.3

Frequencies

GnomAD3 genomes AF: 0.0180 AC: 2746 AN: 152210 Hom.: 45 Cov.: 33

Gnomad AFR AF: 0.00453

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0186

Gnomad ASJ AF: 0.0573

Gnomad EAS AF: 0.0189

Gnomad SAS AF: 0.0418

Gnomad FIN AF: 0.0155

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0224

Gnomad OTH AF: 0.0315

GnomAD4 exome AF: 0.0201 AC: 404 AN: 20070 Hom.: 8 Cov.: 0 AF XY: 0.0219 AC XY: 221 AN XY: 10106

Gnomad4 AFR exome AF: 0.00296

Gnomad4 AMR exome AF: 0.0261

Gnomad4 ASJ exome AF: 0.0385

Gnomad4 EAS exome AF: 0.00458

Gnomad4 SAS exome AF: 0.0335

Gnomad4 FIN exome AF: 0.00923

Gnomad4 NFE exome AF: 0.0181

Gnomad4 OTH exome AF: 0.0222

GnomAD4 genome AF: 0.0180 AC: 2739 AN: 152328 Hom.: 45 Cov.: 33 AF XY: 0.0181 AC XY: 1346 AN XY: 74496

Gnomad4 AFR AF: 0.00450

Gnomad4 AMR AF: 0.0185

Gnomad4 ASJ AF: 0.0573

Gnomad4 EAS AF: 0.0187

Gnomad4 SAS AF: 0.0413

Gnomad4 FIN AF: 0.0155

Gnomad4 NFE AF: 0.0224

Gnomad4 OTH AF: 0.0307

Alfa AF: 0.0199 Hom.: 5

Bravo AF: 0.0166

Asia WGS AF: 0.0200 AC: 71 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	0.67
DANN	Benign	0.63

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: rs8177565; hg19: chr14-77794897;