10-104255223-G-C

Position:

• chr10-104255223-G-C

Variant summary

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

The NM_004832.3(GSTO1):​c.95G>C​(p.Cys32Ser) 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. C32Y) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GSTO1 NM_004832.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.29

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]

GSTO1 (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, 0.836

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSTO1	NM_004832.3	c.95G>C	p.Cys32Ser	missense_variant	2/6	ENST00000369713.10	NP_004823.1
GSTO1	NM_001191003.2	c.11G>C	p.Cys4Ser	missense_variant	2/6		NP_001177932.1
GSTO1	NM_001191002.2	c.95G>C	p.Cys32Ser	missense_variant	2/5		NP_001177931.1
LOC124902497	XR_007062284.1	n.366-6631C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSTO1	ENST00000369713.10	c.95G>C	p.Cys32Ser	missense_variant	2/6	1	NM_004832.3	ENSP00000358727.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	.;.;T;T;T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D;D;D;D
M_CAP	Benign	0.030	D
MetaRNN	Pathogenic	0.84	D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	.;L;L;.;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-9.5	D;D;D;D;D
REVEL	Uncertain	0.45
Sift	Pathogenic	0.0	D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D
Polyphen		1.0	.;.;D;.;.
Vest4		0.95
MutPred		0.65		.;Gain of disorder (P = 0.0165);Gain of disorder (P = 0.0165);.;.;
MVP		0.81
MPC		0.75
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.99
gMVP		0.81

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: rs45529437; hg19: chr10-106014981;