rs11509438

Variant names:

• chr10-104267301-G-A
• rs11509438
• NM_004832.3:c.622G>A

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 49 publications found

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]

ENSG00000302058 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GSTO1	NM_004832.3	c.622G>A	p.Glu208Lys	missense_variant	Exon 6 of 6	ENST00000369713.10	NP_004823.1
GSTO1	NM_001191003.2	c.538G>A	p.Glu180Lys	missense_variant	Exon 6 of 6		NP_001177932.1
GSTO1	NM_001191002.2	c.523G>A	p.Glu175Lys	missense_variant	Exon 5 of 5		NP_001177931.1
LOC124902497	XR_007062284.1	n.365+1252C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTO1	ENST00000369713.10	c.622G>A	p.Glu208Lys	missense_variant	Exon 6 of 6	1	NM_004832.3	ENSP00000358727.5

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

GnomAD2 exomes AF: 0.0368 AC: 9249 AN: 251192 AF XY: 0.0412

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 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

African (AFR) AF: 0.0258 AC: 863 AN: 33458

American (AMR) AF: 0.0153 AC: 684 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.0645 AC: 1684 AN: 26112

East Asian (EAS) AF: 0.00940 AC: 373 AN: 39692

South Asian (SAS) AF: 0.112 AC: 9614 AN: 86184

European-Finnish (FIN) AF: 0.0100 AC: 534 AN: 53414

Middle Eastern (MID) AF: 0.0467 AC: 269 AN: 5766

European-Non Finnish (NFE) AF: 0.0304 AC: 33760 AN: 1111362

Other (OTH) AF: 0.0371 AC: 2238 AN: 60362

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

African (AFR) AF: 0.0250 AC: 1040 AN: 41528

American (AMR) AF: 0.0275 AC: 421 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0594 AC: 206 AN: 3470

East Asian (EAS) AF: 0.00908 AC: 47 AN: 5178

South Asian (SAS) AF: 0.110 AC: 530 AN: 4820

European-Finnish (FIN) AF: 0.00868 AC: 92 AN: 10598

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0297 AC: 2019 AN: 68016

Other (OTH) AF: 0.0298 AC: 63 AN: 2114

Alfa AF: 0.0302 Hom.: 269

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
DEOGEN2	Benign	0.040	.;.;T;T;T
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
MutationAssessor	Benign	0.15	.;.;N;.;.
PhyloP100		-3.5
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
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

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