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14-77326869-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_145870.3(GSTZ1):c.99G>A(p.Thr33=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000836 in 1,607,298 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00063 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00086 ( 0 hom. )

Consequence

GSTZ1
NM_145870.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.56
Variant links:
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 Likely_benign. Variant got -5 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 14-77326869-G-A is Benign according to our data. Variant chr14-77326869-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3040046.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-77326869-G-A is described in Lovd as [Likely_benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.56 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GSTZ1NM_145870.3 linkuse as main transcriptc.99G>A p.Thr33= synonymous_variant 3/9 ENST00000216465.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GSTZ1ENST00000216465.10 linkuse as main transcriptc.99G>A p.Thr33= synonymous_variant 3/91 NM_145870.3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000631
AC:
96
AN:
152214
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000338
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000393
Gnomad ASJ
AF:
0.00173
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000999
Gnomad OTH
AF:
0.000959
GnomAD3 exomes
AF:
0.000596
AC:
143
AN:
239762
Hom.:
0
AF XY:
0.000672
AC XY:
87
AN XY:
129478
show subpopulations
Gnomad AFR exome
AF:
0.000200
Gnomad AMR exome
AF:
0.000505
Gnomad ASJ exome
AF:
0.000719
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000483
Gnomad NFE exome
AF:
0.00106
Gnomad OTH exome
AF:
0.000169
GnomAD4 exome
AF:
0.000857
AC:
1247
AN:
1454966
Hom.:
0
Cov.:
30
AF XY:
0.000902
AC XY:
652
AN XY:
723010
show subpopulations
Gnomad4 AFR exome
AF:
0.000150
Gnomad4 AMR exome
AF:
0.000522
Gnomad4 ASJ exome
AF:
0.000694
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000566
Gnomad4 NFE exome
AF:
0.00103
Gnomad4 OTH exome
AF:
0.000798
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000630
AC:
96
AN:
152332
Hom.:
0
Cov.:
33
AF XY:
0.000550
AC XY:
41
AN XY:
74490
show subpopulations
Gnomad4 AFR
AF:
0.000337
Gnomad4 AMR
AF:
0.000392
Gnomad4 ASJ
AF:
0.00173
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000999
Gnomad4 OTH
AF:
0.000949
Alfa
AF:
0.000900
Hom.:
0
Bravo
AF:
0.000608
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

GSTZ1-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesSep 23, 2019This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.76
Cadd
Benign
0.30
Dann
Benign
0.53

Splicing

Name
Calibrated prediction
Score
Prediction
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs140889171; hg19: chr14-77793212; COSMIC: COSV53622814; COSMIC: COSV53622814; API