chr6-52794240-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_145740.5(GSTA1):c.299C>A(p.Ala100Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
GSTA1
NM_145740.5 missense
NM_145740.5 missense
Scores
1
18
Clinical Significance
Conservation
PhyloP100: -0.383
Genes affected
GSTA1 (HGNC:4626): (glutathione S-transferase alpha 1) This gene encodes a member of a family of enzymes that function to add glutathione to target electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. This action is an important step in detoxification of these compounds. This subfamily of enzymes has a particular role in protecting cells from reactive oxygen species and the products of peroxidation. Polymorphisms in this gene influence the ability of individuals to metabolize different drugs. This gene is located in a cluster of similar genes and pseudogenes on chromosome 6. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.28602064).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GSTA1 | NM_145740.5 | c.299C>A | p.Ala100Glu | missense_variant | 5/7 | ENST00000334575.6 | |
GSTA1 | NM_001319059.2 | c.20C>A | p.Ala7Glu | missense_variant | 4/6 | ||
GSTA1 | XM_005249034.5 | c.299C>A | p.Ala100Glu | missense_variant | 5/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GSTA1 | ENST00000334575.6 | c.299C>A | p.Ala100Glu | missense_variant | 5/7 | 1 | NM_145740.5 | P1 | |
GSTA1 | ENST00000476213.1 | n.353C>A | non_coding_transcript_exon_variant | 4/4 | 5 | ||||
GSTA1 | ENST00000493331.5 | n.196C>A | non_coding_transcript_exon_variant | 3/5 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251328Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135818
GnomAD3 exomes
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1
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251328
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AN XY:
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000137 AC: 2AN: 1461232Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 726972
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
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2
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1461232
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32
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AN XY:
726972
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ExAC
?
AF:
AC:
1
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 04, 2024 | The c.299C>A (p.A100E) alteration is located in exon 5 (coding exon 4) of the GSTA1 gene. This alteration results from a C to A substitution at nucleotide position 299, causing the alanine (A) at amino acid position 100 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Loss of catalytic residue at A100 (P = 0.1015);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at