rs11509438

chr10-104267301-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004832.3(GSTO1):c.622G>A(p.Glu208Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0338 in 1,613,266 control chromosomes in the GnomAD database, including 1,393 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.029 (96 hom., cov: 32)
  • Exomes 𝑓: 0.034 (1297 hom.)
• Consequence: GSTO1 NM_004832.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.53

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0012832582).
• 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.622G>A	p.Glu208Lys	missense_variant	6/6	ENST00000369713.10
LOC124902497	XR_007062284.1	n.365+1252C>T		intron_variant, non_coding_transcript_variant
GSTO1	NM_001191003.2	c.538G>A	p.Glu180Lys	missense_variant	6/6
GSTO1	NM_001191002.2	c.523G>A	p.Glu175Lys	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTO1	ENST00000369713.10	c.622G>A	p.Glu208Lys	missense_variant	6/6	1	NM_004832.3	P1

Frequencies

GnomAD3 genomes AF: 0.0291 AC: 4424 AN: 152114 Hom.: 96 Cov.: 32

Gnomad AFR AF: 0.0249

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0275

Gnomad ASJ AF: 0.0594

Gnomad EAS AF: 0.00906

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.00868

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0297

Gnomad OTH AF: 0.0301

GnomAD3 exomes AF: 0.0368 AC: 9249 AN: 251192 Hom.: 339 AF XY: 0.0412 AC XY: 5596 AN XY: 135784

Gnomad AFR exome AF: 0.0249

Gnomad AMR exome AF: 0.0149

Gnomad ASJ exome AF: 0.0641

Gnomad EAS exome AF: 0.0116

Gnomad SAS exome AF: 0.116

Gnomad FIN exome AF: 0.00799

Gnomad NFE exome AF: 0.0311

Gnomad OTH exome AF: 0.0363

GnomAD4 exome AF: 0.0342 AC: 50019 AN: 1461034 Hom.: 1297 Cov.: 30 AF XY: 0.0367 AC XY: 26681 AN XY: 726900

Gnomad4 AFR exome AF: 0.0258

Gnomad4 AMR exome AF: 0.0153

Gnomad4 ASJ exome AF: 0.0645

Gnomad4 EAS exome AF: 0.00940

Gnomad4 SAS exome AF: 0.112

Gnomad4 FIN exome AF: 0.0100

Gnomad4 NFE exome AF: 0.0304

Gnomad4 OTH exome AF: 0.0371

GnomAD4 genome AF: 0.0291 AC: 4435 AN: 152232 Hom.: 96 Cov.: 32 AF XY: 0.0291 AC XY: 2164 AN XY: 74430

Gnomad4 AFR AF: 0.0250

Gnomad4 AMR AF: 0.0275

Gnomad4 ASJ AF: 0.0594

Gnomad4 EAS AF: 0.00908

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.00868

Gnomad4 NFE AF: 0.0297

Gnomad4 OTH AF: 0.0298

Alfa AF: 0.0313 Hom.: 132

Bravo AF: 0.0283

TwinsUK AF: 0.0302 AC: 112

ALSPAC AF: 0.0332 AC: 128

ESP6500AA AF: 0.0288 AC: 127

ESP6500EA AF: 0.0299 AC: 257

ExAC AF: 0.0377 AC: 4581

Asia WGS AF: 0.0600 AC: 210 AN: 3478

EpiCase AF: 0.0314

EpiControl AF: 0.0345

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.57
Cadd	Benign	0.19
Dann	Benign	0.76
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.18	T;T;T;T;T
MetaRNN	Benign	0.0013	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.030	N;N;N;N;N
REVEL	Benign	0.093
Sift	Benign	0.52	T;T;T;T;T
Sift4G	Benign	0.41	T;T;T;T;T
Polyphen		0.0020	.;.;B;.;.
Vest4		0.078
MPC		0.18
ClinPred		0.0013	T
GERP RS		-7.5
Varity_R		0.18
gMVP		0.32

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: rs11509438; hg19: chr10-106027059; COSMIC: COSV58539916; COSMIC: COSV58539916;