rs8016187

Positions:

• chr14-77324529-T-A
• chr14-77324529-T-C

Variant summary

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

The NM_145870.3(GSTZ1):​c.16-341T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 1,387,252 control chromosomes in the GnomAD database, including 59,162 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 0.24 (5183 hom., cov: 32)
  • Exomes 𝑓: 0.29 (53979 hom.)
• Consequence: GSTZ1 NM_145870.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890

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 (EAS) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSTZ1	NM_145870.3	c.16-341T>A		intron_variant		ENST00000216465.10	NP_665877.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSTZ1	ENST00000216465.10	c.16-341T>A		intron_variant		1	NM_145870.3	ENSP00000216465.5

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35938 AN: 151952 Hom.: 5172 Cov.: 32

Gnomad AFR AF: 0.0831

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.220

GnomAD4 exome AF: 0.288 AC: 355542 AN: 1235184 Hom.: 53979 Cov.: 18 AF XY: 0.285 AC XY: 175720 AN XY: 616836

Gnomad4 AFR exome AF: 0.0769

Gnomad4 AMR exome AF: 0.178

Gnomad4 ASJ exome AF: 0.277

Gnomad4 EAS exome AF: 0.455

Gnomad4 SAS exome AF: 0.175

Gnomad4 FIN exome AF: 0.388

Gnomad4 NFE exome AF: 0.300

Gnomad4 OTH exome AF: 0.273

GnomAD4 genome AF: 0.236 AC: 35955 AN: 152068 Hom.: 5183 Cov.: 32 AF XY: 0.239 AC XY: 17733 AN XY: 74310

Gnomad4 AFR AF: 0.0831

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.281

Gnomad4 EAS AF: 0.438

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.393

Gnomad4 NFE AF: 0.302

Gnomad4 OTH AF: 0.227

Alfa AF: 0.279 Hom.: 828

Bravo AF: 0.217

Asia WGS AF: 0.308 AC: 1066 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	10
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs8016187; hg19: chr14-77790872; COSMIC: COSV53623088; COSMIC: COSV53623088;