rs156697

Positions:

• chr10-104279427-A-G
• chr10-104279427-A-T

Variant summary

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

The NM_183239.2(GSTO2):​c.424A>G​(p.Asn142Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 1,612,916 control chromosomes in the GnomAD database, including 109,695 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 0.45 (17858 hom., cov: 31)
  • Exomes 𝑓: 0.35 (91837 hom.)
• Consequence: GSTO2 NM_183239.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.575

Genes affected

GSTO2 (HGNC:23064): (glutathione S-transferase omega 2) The protein encoded by this gene is an omega class glutathione S-transferase (GST). GSTs are involved in the metabolism of xenobiotics and carcinogens. Four transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.1534677E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSTO2	NM_183239.2	c.424A>G	p.Asn142Asp	missense_variant	5/7	ENST00000338595.7	NP_899062.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSTO2	ENST00000338595.7	c.424A>G	p.Asn142Asp	missense_variant	5/7	1	NM_183239.2	ENSP00000345023	P1

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67758 AN: 151886 Hom.: 17810 Cov.: 31

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.428

GnomAD3 exomes AF: 0.348 AC: 87337 AN: 251258 Hom.: 17067 AF XY: 0.344 AC XY: 46753 AN XY: 135800

Gnomad AFR exome AF: 0.749

Gnomad AMR exome AF: 0.239

Gnomad ASJ exome AF: 0.421

Gnomad EAS exome AF: 0.239

Gnomad SAS exome AF: 0.332

Gnomad FIN exome AF: 0.318

Gnomad NFE exome AF: 0.343

Gnomad OTH exome AF: 0.360

GnomAD4 exome AF: 0.347 AC: 506293 AN: 1460912 Hom.: 91837 Cov.: 35 AF XY: 0.345 AC XY: 250879 AN XY: 726796

Gnomad4 AFR exome AF: 0.757

Gnomad4 AMR exome AF: 0.248

Gnomad4 ASJ exome AF: 0.429

Gnomad4 EAS exome AF: 0.258

Gnomad4 SAS exome AF: 0.331

Gnomad4 FIN exome AF: 0.318

Gnomad4 NFE exome AF: 0.341

Gnomad4 OTH exome AF: 0.365

GnomAD4 genome AF: 0.446 AC: 67860 AN: 152004 Hom.: 17858 Cov.: 31 AF XY: 0.439 AC XY: 32614 AN XY: 74316

Gnomad4 AFR AF: 0.741

Gnomad4 AMR AF: 0.327

Gnomad4 ASJ AF: 0.429

Gnomad4 EAS AF: 0.248

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.307

Gnomad4 NFE AF: 0.344

Gnomad4 OTH AF: 0.425

Alfa AF: 0.364 Hom.: 27977

Bravo AF: 0.462

TwinsUK AF: 0.340 AC: 1260

ALSPAC AF: 0.347 AC: 1336

ESP6500AA AF: 0.743 AC: 3273

ESP6500EA AF: 0.341 AC: 2929

ExAC AF: 0.356 AC: 43214

Asia WGS AF: 0.339 AC: 1179 AN: 3478

EpiCase AF: 0.352

EpiControl AF: 0.358

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.6
DANN	Benign	0.30
DEOGEN2	Benign	0.027	T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.00082	N
LIST_S2	Benign	0.058	T;T
MetaRNN	Benign	8.2e-7	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.3	N;.
MutationTaster	Benign	1.0	P;P;P;P;P;P
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.020	N;N
REVEL	Benign	0.046
Sift	Benign	0.61	T;T
Sift4G	Benign	0.87	T;T
Polyphen		0.0	B;.
Vest4		0.019
MPC		0.087
ClinPred		0.00030	T
GERP RS		4.0
Varity_R		0.44
gMVP		0.24

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: rs156697; hg19: chr10-106039185; COSMIC: COSV58537765;