rs780009826

Variant names:

• chr10-104255261-A-C
• rs780009826
• NM_004832.3:c.133A>C

Your query was ambiguous. Multiple possible variants found:

• chr10-104255261-A-C
• chr10-104255261-A-G
• chr10-104255261-A-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.133A>C​(p.Lys45Gln) 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. K45E) 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: 8.66
• 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, 0.921

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.133A>C	p.Lys45Gln	missense	Exon 2 of 6	NP_004823.1	P78417-1
	GSTO1	NM_001191003.2		c.49A>C	p.Lys17Gln	missense	Exon 2 of 6	NP_001177932.1	P78417-3
	GSTO1	NM_001191002.2		c.133A>C	p.Lys45Gln	missense	Exon 2 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.133A>C	p.Lys45Gln	missense	Exon 2 of 6	ENSP00000358727.5	P78417-1
	GSTO1	ENST00000539281.5	TSL:5	c.49A>C	p.Lys17Gln	missense	Exon 2 of 6	ENSP00000441488.1	P78417-3
	GSTO1	ENST00000369710.8	TSL:2	c.133A>C	p.Lys45Gln	missense	Exon 2 of 5	ENSP00000358724.4	P78417-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Benign	0.011	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.92	D
MetaSVM	Benign	-0.77	T
MutationAssessor	Pathogenic	4.3	H
PhyloP100		8.7
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.99	D
Vest4		0.90
MutPred		0.87		Loss of MoRF binding (P = 0.04)
MVP		0.80
MPC		0.68
ClinPred		0.98	D
GERP RS		1.2
PromoterAI		0.041	Neutral
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.7
Varity_R		0.98
gMVP		0.85
Mutation Taster		=81/19	polymorphism

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: rs780009826; hg19: chr10-106015019;