chr10-104255250-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004832.3(GSTO1):ā€‹c.122T>Cā€‹(p.Val41Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000124 in 1,611,956 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000033 ( 0 hom., cov: 32)
Exomes š‘“: 0.000010 ( 0 hom. )

Consequence

GSTO1
NM_004832.3 missense

Scores

1
8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.72
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GSTO1NM_004832.3 linkuse as main transcriptc.122T>C p.Val41Ala missense_variant 2/6 ENST00000369713.10
LOC124902497XR_007062284.1 linkuse as main transcriptn.366-6658A>G intron_variant, non_coding_transcript_variant
GSTO1NM_001191003.2 linkuse as main transcriptc.38T>C p.Val13Ala missense_variant 2/6
GSTO1NM_001191002.2 linkuse as main transcriptc.122T>C p.Val41Ala missense_variant 2/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GSTO1ENST00000369713.10 linkuse as main transcriptc.122T>C p.Val41Ala missense_variant 2/61 NM_004832.3 P1P78417-1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152076
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000774
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000478
AC:
12
AN:
250984
Hom.:
0
AF XY:
0.0000368
AC XY:
5
AN XY:
135780
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000654
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000103
AC:
15
AN:
1459762
Hom.:
0
Cov.:
30
AF XY:
0.00000826
AC XY:
6
AN XY:
726328
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000151
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.000133
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152194
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74408
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000776
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.0000416
ExAC
AF:
0.0000659
AC:
8
Asia WGS
AF:
0.00231
AC:
8
AN:
3478

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 GeneticsJan 24, 2024The c.122T>C (p.V41A) alteration is located in exon 2 (coding exon 2) of the GSTO1 gene. This alteration results from a T to C substitution at nucleotide position 122, causing the valine (V) at amino acid position 41 to be replaced by an alanine (A). 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
Uncertain
0.53
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.14
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.12
.;.;T;T;T
Eigen
Uncertain
0.41
Eigen_PC
Uncertain
0.43
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.84
T;T;T;T;T
M_CAP
Benign
0.022
T
MetaRNN
Uncertain
0.47
T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.28
.;N;N;.;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Benign
0.45
T
PROVEAN
Uncertain
-3.9
D;D;D;D;D
REVEL
Uncertain
0.33
Sift
Uncertain
0.0010
D;T;D;T;T
Sift4G
Benign
0.080
T;T;T;T;T
Polyphen
0.99
.;.;D;.;.
Vest4
0.65
MutPred
0.83
.;Loss of stability (P = 0.0653);Loss of stability (P = 0.0653);.;.;
MVP
0.70
MPC
0.55
ClinPred
0.56
D
GERP RS
5.0
Varity_R
0.86
gMVP
0.70

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: rs781512367; hg19: chr10-106015008; API