chr10-104259701-G-T

Variant names:

• chr10-104259701-G-T
• rs1589844800
• NM_004832.3:c.269G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_004832.3(GSTO1):​c.269G>T​(p.Cys90Phe) variant causes a missense change involving the alteration of a conserved nucleotide. 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: 32)
• Consequence: GSTO1 NM_004832.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.46
• Publications: 0 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.853

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004832.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTO1	NM_004832.3	MANE Select	c.269G>T	p.Cys90Phe	missense	Exon 3 of 6	NP_004823.1	P78417-1
	GSTO1	NM_001191003.2		c.185G>T	p.Cys62Phe	missense	Exon 3 of 6	NP_001177932.1	P78417-3
	GSTO1	NM_001191002.2		c.269G>T	p.Cys90Phe	missense	Exon 3 of 5	NP_001177931.1	P78417-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTO1	ENST00000369713.10	TSL:1 MANE Select	c.269G>T	p.Cys90Phe	missense	Exon 3 of 6	ENSP00000358727.5	P78417-1
	GSTO1	ENST00000539281.5	TSL:5	c.185G>T	p.Cys62Phe	missense	Exon 3 of 6	ENSP00000441488.1	P78417-3
	GSTO1	ENST00000369710.8	TSL:2	c.269G>T	p.Cys90Phe	missense	Exon 3 of 5	ENSP00000358724.4	P78417-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.039	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		7.5
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-11	D
REVEL	Uncertain	0.51
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.85
MutPred		0.52		Loss of helix (P = 0.2022)
MVP		0.84
MPC		0.76
ClinPred		1.0	D
GERP RS		5.7
Varity_R		0.99
gMVP		0.87
Mutation Taster		=38/62	disease causing

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: rs1589844800; hg19: chr10-106019459;