rs776678047
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_145870.3(GSTZ1):c.68-12G>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 0.0000257 in 1,592,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Affects (no stars).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000027 ( 0 hom. )
Consequence
GSTZ1
NM_145870.3 splice_polypyrimidine_tract, intron
NM_145870.3 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.9993
2
Clinical Significance
Conservation
PhyloP100: -0.887
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GSTZ1 | NM_145870.3 | c.68-12G>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.68-12G>A | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_145870.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152168Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000131 AC: 3AN: 229526Hom.: 0 AF XY: 0.0000242 AC XY: 3AN XY: 123858
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GnomAD4 exome AF: 0.0000271 AC: 39AN: 1440680Hom.: 0 Cov.: 27 AF XY: 0.0000321 AC XY: 23AN XY: 715778
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152168Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74314
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ClinVar
Significance: Affects
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Maleylacetoacetate isomerase deficiency Other:1
Affects, no assertion criteria provided | literature only | OMIM | Jul 26, 2017 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 2
DS_AL_spliceai
Position offset: 12
Find out detailed SpliceAI scores and Pangolin per-transcript scores at