rs8177544

Positions:

• chr14-77322445-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSTZ1	NM_145870.3	c.15+1262C>T		intron_variant		ENST00000216465.10	NP_665877.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSTZ1	ENST00000216465.10	c.15+1262C>T		intron_variant		1	NM_145870.3	ENSP00000216465

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

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.0139

Gnomad4 ASJ exome AF: 0.0286

Gnomad4 EAS exome AF: 0.00704

Gnomad4 SAS exome AF: 0.0965

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0389

Gnomad4 OTH exome AF: 0.0533

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

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.0295

Gnomad4 ASJ AF: 0.0239

Gnomad4 EAS AF: 0.00656

Gnomad4 SAS AF: 0.0880

Gnomad4 FIN AF: 0.0225

Gnomad4 NFE AF: 0.0377

Gnomad4 OTH AF: 0.0512

Alfa AF: 0.0382 Hom.: 156

Bravo AF: 0.0652

Asia WGS AF: 0.0540 AC: 189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.5
DANN	Benign	0.69

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: rs8177544; hg19: chr14-77788788;