14-77327849-C-T

Position:

• chr14-77327849-C-T

Variant summary

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

The ENST00000216465.10(GSTZ1):​c.217-63C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,549,428 control chromosomes in the GnomAD database, including 29,440 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 0.15 (2264 hom., cov: 32)
  • Exomes 𝑓: 0.19 (27176 hom.)
• Consequence: GSTZ1 ENST00000216465.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.879

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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSTZ1	NM_145870.3	c.217-63C>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.217-63C>T		intron_variant		1	NM_145870.3	ENSP00000216465

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23453 AN: 151812 Hom.: 2264 Cov.: 32

Gnomad AFR AF: 0.0397

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.170

GnomAD4 exome AF: 0.192 AC: 267711 AN: 1397498 Hom.: 27176 Cov.: 23 AF XY: 0.192 AC XY: 134183 AN XY: 698008

Gnomad4 AFR exome AF: 0.0312

Gnomad4 AMR exome AF: 0.337

Gnomad4 ASJ exome AF: 0.166

Gnomad4 EAS exome AF: 0.252

Gnomad4 SAS exome AF: 0.230

Gnomad4 FIN exome AF: 0.161

Gnomad4 NFE exome AF: 0.187

Gnomad4 OTH exome AF: 0.186

GnomAD4 genome AF: 0.154 AC: 23460 AN: 151930 Hom.: 2264 Cov.: 32 AF XY: 0.158 AC XY: 11699 AN XY: 74264

Gnomad4 AFR AF: 0.0396

Gnomad4 AMR AF: 0.252

Gnomad4 ASJ AF: 0.170

Gnomad4 EAS AF: 0.260

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.170

Alfa AF: 0.189 Hom.: 3876

Bravo AF: 0.159

Asia WGS AF: 0.243 AC: 846 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	13
DANN	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs2287396; hg19: chr14-77794192; COSMIC: COSV53622785; COSMIC: COSV53622785;