10-104263071-AGAG-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PM4_Supporting BP6_Moderate BA1

The NM_004832.3(GSTO1):c.464_465+1del variant causes a inframe deletion change. The variant allele was found at a frequency of 0.0305 in 1,302,596 control chromosomes in the GnomAD database, including 1,111 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.029 (96 hom., cov: 32)
  • Exomes 𝑓: 0.031 (1015 hom.)
• Consequence: GSTO1 NM_004832.3 inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.24

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]

LOC124902497 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_004832.3. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 10-104263071-AGAG-A is Benign according to our data. Variant chr10-104263071-AGAG-A is described in ClinVar as [Likely_benign]. Clinvar id is 3055930.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSTO1	NM_004832.3	c.464_465+1del		inframe_deletion	4/6	ENST00000369713.10
LOC124902497	XR_007062284.1	n.365+5479_365+5481del		intron_variant, non_coding_transcript_variant
GSTO1	NM_001191003.2	c.380_381+1del		inframe_deletion	4/6
GSTO1	NM_001191002.2	c.367-3008_367-3006del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTO1	ENST00000369713.10	c.464_465+1del		inframe_deletion	4/6	1	NM_004832.3	P1

Frequencies

GnomAD3 genomes AF: 0.0290 AC: 4419 AN: 152208 Hom.: 96 Cov.: 32

Gnomad AFR AF: 0.0248

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0275

Gnomad ASJ AF: 0.0597

Gnomad EAS AF: 0.00906

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.00857

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0296

Gnomad OTH AF: 0.0306

GnomAD3 exomes AF: 0.0357 AC: 8506 AN: 238046 Hom.: 306 AF XY: 0.0396 AC XY: 5106 AN XY: 128868

Gnomad AFR exome AF: 0.0245

Gnomad AMR exome AF: 0.0151

Gnomad ASJ exome AF: 0.0639

Gnomad EAS exome AF: 0.0116

Gnomad SAS exome AF: 0.113

Gnomad FIN exome AF: 0.00793

Gnomad NFE exome AF: 0.0305

Gnomad OTH exome AF: 0.0352

GnomAD4 exome AF: 0.0307 AC: 35327 AN: 1150270 Hom.: 1015 AF XY: 0.0338 AC XY: 19780 AN XY: 585726

Gnomad4 AFR exome AF: 0.0228

Gnomad4 AMR exome AF: 0.0156

Gnomad4 ASJ exome AF: 0.0629

Gnomad4 EAS exome AF: 0.00911

Gnomad4 SAS exome AF: 0.107

Gnomad4 FIN exome AF: 0.00991

Gnomad4 NFE exome AF: 0.0258

Gnomad4 OTH exome AF: 0.0336

GnomAD4 genome AF: 0.0291 AC: 4428 AN: 152326 Hom.: 96 Cov.: 32 AF XY: 0.0290 AC XY: 2160 AN XY: 74478

Gnomad4 AFR AF: 0.0249

Gnomad4 AMR AF: 0.0274

Gnomad4 ASJ AF: 0.0597

Gnomad4 EAS AF: 0.00908

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.00857

Gnomad4 NFE AF: 0.0297

Gnomad4 OTH AF: 0.0302

Alfa AF: 0.00979 Hom.: 21

Bravo AF: 0.0283

Asia WGS AF: 0.0600 AC: 209 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

GSTO1-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 31, 2023

This variant is classified as likely 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

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

Other links and lift over

dbSNP: rs72323784; hg19: chr10-106022829;