Variant 10-104259764-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_004832.3(GSTO1):c.332C>G(p.Ala111Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,098 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

GSTO1
NM_004832.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.57

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]

GSTO1 links:

LOC124902497 (HGNC:):

LOC124902497 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.941

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GSTO1	NM_004832.3 linkuse as main transcript	c.332C>G	p.Ala111Gly	missense_variant	3/6	ENST00000369713.10
LOC124902497	XR_007062284.1 linkuse as main transcript	n.365+8789G>C		intron_variant, non_coding_transcript_variant
GSTO1	NM_001191003.2 linkuse as main transcript	c.248C>G	p.Ala83Gly	missense_variant	3/6
GSTO1	NM_001191002.2 linkuse as main transcript	c.332C>G	p.Ala111Gly	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTO1	ENST00000369713.10 linkuse as main transcript	c.332C>G	p.Ala111Gly	missense_variant	3/6	1	NM_004832.3	P1	P78417-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251384

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461098

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726918

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

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

Jun 24, 2022

The c.332C>G (p.A111G) alteration is located in exon 3 (coding exon 3) of the GSTO1 gene. This alteration results from a C to G substitution at nucleotide position 332, causing the alanine (A) at amino acid position 111 to be replaced by a glycine (G). 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

0.37

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.080

Cadd

Pathogenic

Dann

Uncertain

1.0

Eigen

Pathogenic

0.98

Eigen_PC

Pathogenic

0.92

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.97

D;D;D;D;D

M_CAP

Benign

0.063

MetaRNN

Pathogenic

0.94

D;D;D;D;D

MetaSVM

Benign

-0.44

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-4.0

D;D;D;D;D

REVEL

Uncertain

0.56

Sift

Uncertain

0.0050

D;D;D;D;D

Sift4G

Uncertain

0.0090

D;D;D;D;D

Polyphen

1.0

.;.;D;.;.

Vest4

0.78

MutPred

0.81

.;Gain of catalytic residue at P107 (P = 0.0678);Gain of catalytic residue at P107 (P = 0.0678);.;.;

MVP

0.77

MPC

0.67

ClinPred

0.98

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.91

gMVP

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over