chr10-104263010-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004832.3(GSTO1):​c.398G>A​(p.Ser133Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000402 in 1,541,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

GSTO1
NM_004832.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.712
Variant links:
Genes affected
GSTO1 (HGNC:13312): (glutathione S-transferase omega 1) The protein encoded by this gene is an omega class glutathione S-transferase (GST) with glutathione-dependent thiol transferase and dehydroascorbate reductase activities. GSTs are involved in the metabolism of xenobiotics and carcinogens. The encoded protein acts as a homodimer and is found in the cytoplasm. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.04726714).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GSTO1NM_004832.3 linkuse as main transcriptc.398G>A p.Ser133Asn missense_variant 4/6 ENST00000369713.10
LOC124902497XR_007062284.1 linkuse as main transcriptn.365+5543C>T intron_variant, non_coding_transcript_variant
GSTO1NM_001191003.2 linkuse as main transcriptc.314G>A p.Ser105Asn missense_variant 4/6
GSTO1NM_001191002.2 linkuse as main transcriptc.367-3074G>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GSTO1ENST00000369713.10 linkuse as main transcriptc.398G>A p.Ser133Asn missense_variant 4/61 NM_004832.3 P1P78417-1

Frequencies

GnomAD3 genomes
AF:
0.000105
AC:
16
AN:
152154
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000524
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000244
AC:
6
AN:
246186
Hom.:
0
AF XY:
0.0000225
AC XY:
3
AN XY:
133136
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000299
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000447
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000331
AC:
46
AN:
1388966
Hom.:
0
Cov.:
23
AF XY:
0.0000389
AC XY:
27
AN XY:
694912
show subpopulations
Gnomad4 AFR exome
AF:
0.0000309
Gnomad4 AMR exome
AF:
0.000184
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000267
Gnomad4 OTH exome
AF:
0.000138
GnomAD4 genome
AF:
0.000105
AC:
16
AN:
152154
Hom.:
0
Cov.:
32
AF XY:
0.000121
AC XY:
9
AN XY:
74330
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000524
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000580
Hom.:
0
Bravo
AF:
0.000268
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000330
AC:
4
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 submitterclinical testingAmbry GeneticsNov 14, 2023The c.398G>A (p.S133N) alteration is located in exon 4 (coding exon 4) of the GSTO1 gene. This alteration results from a G to A substitution at nucleotide position 398, causing the serine (S) at amino acid position 133 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.43
T
BayesDel_noAF
Benign
-0.73
CADD
Benign
5.3
DANN
Benign
0.38
DEOGEN2
Benign
0.052
.;T;T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.085
N
LIST_S2
Benign
0.21
T;T;T
M_CAP
Benign
0.0047
T
MetaRNN
Benign
0.047
T;T;T
MetaSVM
Benign
-0.90
T
MutationAssessor
Benign
0.96
.;L;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.30
T
PROVEAN
Benign
-0.51
N;N;N
REVEL
Benign
0.044
Sift
Benign
0.42
T;T;T
Sift4G
Benign
0.39
T;T;T
Polyphen
0.0070
.;B;.
Vest4
0.079
MVP
0.31
MPC
0.15
ClinPred
0.023
T
GERP RS
-0.80
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.089
gMVP
0.37

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

LitVar

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

Other links and lift over

dbSNP: rs139445649; hg19: chr10-106022768; API