10-104279397-G-T

Position:

• chr10-104279397-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_183239.2(GSTO2):​c.394G>T​(p.Val132Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GSTO2 NM_183239.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.513

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061935455).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSTO2	NM_183239.2	c.394G>T	p.Val132Leu	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.394G>T	p.Val132Leu	missense_variant	5/7	1	NM_183239.2	ENSP00000345023.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 30, 2022

The c.394G>T (p.V132L) alteration is located in exon 5 (coding exon 4) of the GSTO2 gene. This alteration results from a G to T substitution at nucleotide position 394, causing the valine (V) at amino acid position 132 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	6.4
DANN	Benign	0.60
DEOGEN2	Benign	0.029	T;.
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.62	T;T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.062	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.28	N;.
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.16	N;N
REVEL	Benign	0.056
Sift	Benign	0.84	T;T
Sift4G	Benign	0.65	T;T
Polyphen		0.0	B;.
Vest4		0.085
MutPred		0.39		Loss of catalytic residue at V132 (P = 0.0779);.;
MVP		0.31
MPC		0.076
ClinPred		0.059	T
GERP RS		1.4
Varity_R		0.042
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-106039155;