14-77330415-C-T

Position:

• chr14-77330415-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.524+56C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0461 in 1,393,758 control chromosomes in the GnomAD database, including 1,756 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 0.039 (151 hom., cov: 32)
  • Exomes 𝑓: 0.047 (1605 hom.)
• Consequence: GSTZ1 NM_145870.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSTZ1	NM_145870.3	c.524+56C>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.524+56C>T		intron_variant		1	NM_145870.3	ENSP00000216465.5

Frequencies

GnomAD3 genomes AF: 0.0386 AC: 5876 AN: 152184 Hom.: 151 Cov.: 32

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.00879

Gnomad AMR AF: 0.0373

Gnomad ASJ AF: 0.0554

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0141

Gnomad FIN AF: 0.0512

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0582

Gnomad OTH AF: 0.0407

GnomAD4 exome AF: 0.0470 AC: 58334 AN: 1241456 Hom.: 1605 AF XY: 0.0463 AC XY: 29071 AN XY: 628360

Gnomad4 AFR exome AF: 0.00924

Gnomad4 AMR exome AF: 0.0293

Gnomad4 ASJ exome AF: 0.0507

Gnomad4 EAS exome AF: 0.000103

Gnomad4 SAS exome AF: 0.0114

Gnomad4 FIN exome AF: 0.0455

Gnomad4 NFE exome AF: 0.0545

Gnomad4 OTH exome AF: 0.0431

GnomAD4 genome AF: 0.0386 AC: 5872 AN: 152302 Hom.: 151 Cov.: 32 AF XY: 0.0369 AC XY: 2750 AN XY: 74472

Gnomad4 AFR AF: 0.0104

Gnomad4 AMR AF: 0.0371

Gnomad4 ASJ AF: 0.0554

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0137

Gnomad4 FIN AF: 0.0512

Gnomad4 NFE AF: 0.0582

Gnomad4 OTH AF: 0.0408

Alfa AF: 0.0508 Hom.: 46

Bravo AF: 0.0369

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.35
DANN	Benign	0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs8177573; hg19: chr14-77796758;