Variant chr10-104263031-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_004832.3(GSTO1):c.419C>A(p.Ala140Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 1,519,098 control chromosomes in the GnomAD database, including 58,948 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.24 ( 4921 hom., cov: 33)

Exomes 𝑓: 0.27 ( 54027 hom. )

Consequence

GSTO1
NM_004832.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.992

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015232861).

BP6

Variant 10-104263031-C-A is Benign according to our data. Variant chr10-104263031-C-A is described in ClinVar as [Benign]. Clinvar id is 3059603.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GSTO1	NM_004832.3 linkuse as main transcript	c.419C>A	p.Ala140Asp	missense_variant	4/6	ENST00000369713.10
LOC124902497	XR_007062284.1 linkuse as main transcript	n.365+5522G>T		intron_variant, non_coding_transcript_variant
GSTO1	NM_001191003.2 linkuse as main transcript	c.335C>A	p.Ala112Asp	missense_variant	4/6
GSTO1	NM_001191002.2 linkuse as main transcript	c.367-3053C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTO1	ENST00000369713.10 linkuse as main transcript	c.419C>A	p.Ala140Asp	missense_variant	4/6	1	NM_004832.3	P1	P78417-1

Frequencies

GnomAD3 genomes

AF:

0.236

AC:

35883

AN:

152060

Hom.:

4920

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.207

Gnomad AMR

AF:

0.237

Gnomad ASJ

AF:

0.337

Gnomad EAS

AF:

0.138

Gnomad SAS

AF:

0.205

Gnomad FIN

AF:

0.268

Gnomad MID

AF:

0.347

Gnomad NFE

AF:

0.315

Gnomad OTH

AF:

0.274

GnomAD3 exomes

AF:

0.248

AC:

60720

AN:

245134

Hom.:

8488

AF XY:

0.254

AC XY:

33683

AN XY:

132524

show subpopulations

Gnomad AFR exome

AF:

0.0976

Gnomad AMR exome

AF:

0.178

Gnomad ASJ exome

AF:

0.315

Gnomad EAS exome

AF:

0.135

Gnomad SAS exome

AF:

0.193

Gnomad FIN exome

AF:

0.274

Gnomad NFE exome

AF:

0.310

Gnomad OTH exome

AF:

0.282

GnomAD4 exome

AF:

0.272

AC:

372389

AN:

1366918

Hom.:

54027

Cov.:

AF XY:

0.273

AC XY:

186857

AN XY:

684390

show subpopulations

Gnomad4 AFR exome

AF:

0.0884

Gnomad4 AMR exome

AF:

0.183

Gnomad4 ASJ exome

AF:

0.317

Gnomad4 EAS exome

AF:

0.127

Gnomad4 SAS exome

AF:

0.195

Gnomad4 FIN exome

AF:

0.274

Gnomad4 NFE exome

AF:

0.293

Gnomad4 OTH exome

AF:

0.261

GnomAD4 genome

AF:

0.236

AC:

35893

AN:

152180

Hom.:

4921

Cov.:

AF XY:

0.233

AC XY:

17319

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.103

Gnomad4 AMR

AF:

0.236

Gnomad4 ASJ

AF:

0.337

Gnomad4 EAS

AF:

0.138

Gnomad4 SAS

AF:

0.207

Gnomad4 FIN

AF:

0.268

Gnomad4 NFE

AF:

0.315

Gnomad4 OTH

AF:

0.271

Alfa

AF:

0.301

Hom.:

18522

Bravo

AF:

0.229

TwinsUK

AF:

0.313

AC:

1162

ALSPAC

AF:

0.314

AC:

1212

ESP6500AA

AF:

0.109

AC:

481

ESP6500EA

AF:

0.310

AC:

2665

ExAC

AF:

0.252

AC:

30562

Asia WGS

AF:

0.161

AC:

561

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

GSTO1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.022

.;T;T

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.73

T;T;T

MetaRNN

Benign

0.0015

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.49

.;N;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.82

N;N;N

REVEL

Benign

0.053

Sift

Uncertain

0.015

D;D;T

Sift4G

Benign

0.44

T;T;T

Polyphen

0.23

.;B;.

Vest4

0.11

MPC

0.24

ClinPred

0.0080

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.35

gMVP

0.51

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.

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