14-77330298-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_145870.3(GSTZ1):c.475-12G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 1,606,326 control chromosomes in the GnomAD database, including 275,162 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.65 (33817 hom., cov: 32)
  • Exomes 𝑓: 0.57 (241345 hom.)
• Consequence: GSTZ1 NM_145870.3 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00003185
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 14-77330298-G-A is Benign according to our data. Variant chr14-77330298-G-A is described in ClinVar as [Benign]. Clinvar id is 1276008.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSTZ1	NM_145870.3	c.475-12G>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000216465.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTZ1	ENST00000216465.10	c.475-12G>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_145870.3

Frequencies

GnomAD3 genomes AF: 0.651 AC: 98867 AN: 151946 Hom.: 33763 Cov.: 32

Gnomad AFR AF: 0.884

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.602

GnomAD3 exomes AF: 0.572 AC: 143713 AN: 251466 Hom.: 42155 AF XY: 0.565 AC XY: 76850 AN XY: 135906

Gnomad AFR exome AF: 0.891

Gnomad AMR exome AF: 0.524

Gnomad ASJ exome AF: 0.542

Gnomad EAS exome AF: 0.515

Gnomad SAS exome AF: 0.529

Gnomad FIN exome AF: 0.585

Gnomad NFE exome AF: 0.561

Gnomad OTH exome AF: 0.571

GnomAD4 exome AF: 0.573 AC: 832826 AN: 1454262 Hom.: 241345 Cov.: 32 AF XY: 0.570 AC XY: 412845 AN XY: 723954

Gnomad4 AFR exome AF: 0.894

Gnomad4 AMR exome AF: 0.520

Gnomad4 ASJ exome AF: 0.547

Gnomad4 EAS exome AF: 0.542

Gnomad4 SAS exome AF: 0.533

Gnomad4 FIN exome AF: 0.587

Gnomad4 NFE exome AF: 0.569

Gnomad4 OTH exome AF: 0.580

GnomAD4 genome AF: 0.651 AC: 98983 AN: 152064 Hom.: 33817 Cov.: 32 AF XY: 0.644 AC XY: 47884 AN XY: 74326

Gnomad4 AFR AF: 0.884

Gnomad4 AMR AF: 0.564

Gnomad4 ASJ AF: 0.546

Gnomad4 EAS AF: 0.533

Gnomad4 SAS AF: 0.548

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.566

Gnomad4 OTH AF: 0.605

Alfa AF: 0.575 Hom.: 26328

Bravo AF: 0.659

Asia WGS AF: 0.558 AC: 1938 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 13, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.057
Dann	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000032
dbscSNV1_RF	Benign	0.0
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: rs731346; hg19: chr14-77796641;