chr10-104259701-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_004832.3(GSTO1):​c.269G>C​(p.Cys90Ser) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C90F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GSTO1 NM_004832.3 missense
• Clinical Significance: Not reported in ClinVar
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.837

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>C	p.Cys90Ser	missense	Exon 3 of 6	NP_004823.1	P78417-1
	GSTO1	NM_001191003.2		c.185G>C	p.Cys62Ser	missense	Exon 3 of 6	NP_001177932.1	P78417-3
	GSTO1	NM_001191002.2		c.269G>C	p.Cys90Ser	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>C	p.Cys90Ser	missense	Exon 3 of 6	ENSP00000358727.5	P78417-1
	GSTO1	ENST00000539281.5	TSL:5	c.185G>C	p.Cys62Ser	missense	Exon 3 of 6	ENSP00000441488.1	P78417-3
	GSTO1	ENST00000369710.8	TSL:2	c.269G>C	p.Cys90Ser	missense	Exon 3 of 5	ENSP00000358724.4	P78417-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Uncertain	0.038	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	27
DANN	Benign	0.97
DEOGEN2	Benign	0.14	T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.016	T
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		7.5
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-10	D
REVEL	Benign	0.29
Sift	Benign	0.077	T
Sift4G	Benign	0.10	T
Polyphen		1.0	D
Vest4		0.57
MutPred		0.65		Gain of disorder (P = 0.0058)
MVP		0.87
MPC		0.31
ClinPred		1.0	D
GERP RS		5.7
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.8
Varity_R		0.96
gMVP		0.81
Mutation Taster		=40/60	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;