10-104263070-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_004832.3(GSTO1):c.458T>G(p.Leu153Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GSTO1 NM_004832.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.50

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.78

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSTO1	NM_004832.3	c.458T>G	p.Leu153Arg	missense_variant	4/6	ENST00000369713.10
LOC124902497	XR_007062284.1	n.365+5483A>C		intron_variant, non_coding_transcript_variant
GSTO1	NM_001191003.2	c.374T>G	p.Leu125Arg	missense_variant	4/6
GSTO1	NM_001191002.2	c.367-3014T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTO1	ENST00000369713.10	c.458T>G	p.Leu153Arg	missense_variant	4/6	1	NM_004832.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 17

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

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

Sep 23, 2023

The c.458T>G (p.L153R) alteration is located in exon 4 (coding exon 4) of the GSTO1 gene. This alteration results from a T to G substitution at nucleotide position 458, causing the leucine (L) at amino acid position 153 to be replaced by an arginine (R). 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	Pathogenic	0.80
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
Cadd	Pathogenic	27
Dann	Uncertain	1.0
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.68	T;T;T
M_CAP	Benign	0.081	D
MetaRNN	Pathogenic	0.78	D;D;D
MetaSVM	Benign	-0.62	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-4.3	D;D;D
REVEL	Uncertain	0.48
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		1.0	.;D;.
Vest4		0.89
MutPred		0.64		.;Gain of disorder (P = 0.0178);.;
MVP		0.79
MPC		0.81
ClinPred		1.0	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.98
gMVP		0.93

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: rs1318102193; hg19: chr10-106022828;