GeneBe

rs1765458849

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_000847.5(GSTA3):​c.615G>T​(p.Lys205Asn) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

GSTA3
NM_000847.5 missense

Scores

3
4
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0840
Variant links:
Genes affected
GSTA3 (HGNC:4628): (glutathione S-transferase alpha 3) Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. These enzymes are involved in cellular defense against toxic, carcinogenic, and pharmacologically active electrophilic compounds. At present, eight distinct classes of the soluble cytoplasmic mammalian glutathione S-transferases have been identified: alpha, kappa, mu, omega, pi, sigma, theta and zeta. This gene encodes a glutathione S-tranferase belonging to the alpha class genes that are located in a cluster mapped to chromosome 6. Genes of the alpha class are highly related and encode enzymes with glutathione peroxidase activity. However, during evolution, this alpha class gene diverged accumulating mutations in the active site that resulted in differences in substrate specificity and catalytic activity. The enzyme encoded by this gene catalyzes the double bond isomerization of precursors for progesterone and testosterone during the biosynthesis of steroid hormones. An additional transcript variant has been identified, but its full length sequence has not been determined. [provided by RefSeq, Jul 2008]

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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=0.31153876).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GSTA3NM_000847.5 linkc.615G>T p.Lys205Asn missense_variant Exon 7 of 7 ENST00000211122.4 NP_000838.3 Q16772

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GSTA3ENST00000211122.4 linkc.615G>T p.Lys205Asn missense_variant Exon 7 of 7 1 NM_000847.5 ENSP00000211122.3 Q16772
GSTA3ENST00000370968.5 linkc.465G>T p.Lys155Asn missense_variant Exon 6 of 6 1 ENSP00000360007.1 Q5JW85

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.87
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
12
DANN
Benign
0.93
DEOGEN2
Benign
0.31
.;T
Eigen
Benign
-0.78
Eigen_PC
Benign
-0.91
FATHMM_MKL
Uncertain
0.82
D
LIST_S2
Benign
0.83
T;T
M_CAP
Benign
0.0095
T
MetaRNN
Benign
0.31
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Pathogenic
2.9
.;M
PrimateAI
Uncertain
0.56
T
PROVEAN
Pathogenic
-4.5
D;D
REVEL
Benign
0.16
Sift
Uncertain
0.0050
D;D
Sift4G
Uncertain
0.043
D;D
Polyphen
0.56
.;P
Vest4
0.43
MutPred
0.37
.;Loss of methylation at K205 (P = 0.0043);
MVP
0.19
MPC
0.081
ClinPred
0.98
D
GERP RS
0.39
Varity_R
0.82
gMVP
0.26

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-52761658; API