chr10-104274940-C-G

Variant names:

• chr10-104274940-C-G
• rs775086288
• NM_183239.2:c.25C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_183239.2(GSTO2):​c.25C>G​(p.Leu9Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,451,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: GSTO2 NM_183239.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.463
• Publications: 0 publications found

Genes affected

GSTO2 (HGNC:23064): (glutathione S-transferase omega 2) The protein encoded by this gene is an omega class glutathione S-transferase (GST). GSTs are involved in the metabolism of xenobiotics and carcinogens. Four transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19602591).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_183239.2. 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
	GSTO2	NM_183239.2	MANE Select	c.25C>G	p.Leu9Val	missense	Exon 2 of 7	NP_899062.1	Q9H4Y5-1
	GSTO2	NM_001191013.2		c.25C>G	p.Leu9Val	missense	Exon 2 of 6	NP_001177942.1	Q9H4Y5-2
	GSTO2	NM_001191014.2		c.-336C>G		upstream_gene	N/A	NP_001177943.1	Q9H4Y5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTO2	ENST00000338595.7	TSL:1 MANE Select	c.25C>G	p.Leu9Val	missense	Exon 2 of 7	ENSP00000345023.1	Q9H4Y5-1
	GSTO2	ENST00000912037.1		c.25C>G	p.Leu9Val	missense	Exon 2 of 7	ENSP00000582096.1
	GSTO2	ENST00000912039.1		c.25C>G	p.Leu9Val	missense	Exon 1 of 6	ENSP00000582098.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000131 AC: 3 AN: 228240 AF XY: 0.0000160

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000964

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000110 AC: 16 AN: 1451224 Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10 AN XY: 722034

African (AFR) AF: 0.00 AC: 0 AN: 32630

American (AMR) AF: 0.00 AC: 0 AN: 41614

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25680

East Asian (EAS) AF: 0.00 AC: 0 AN: 39180

South Asian (SAS) AF: 0.000118 AC: 10 AN: 84700

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53020

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5732

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108780

Other (OTH) AF: 0.0000668 AC: 4 AN: 59888

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000508 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

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	Benign	0.15
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	14
DANN	Benign	0.93
DEOGEN2	Benign	0.090	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		-0.46
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.13
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.013	D
Polyphen		0.72	P
Vest4		0.22
MutPred		0.20		Gain of MoRF binding (P = 0.0728)
MVP		0.38
MPC		0.24
ClinPred		0.57	D
GERP RS		-5.0
PromoterAI		0.067	Neutral
Varity_R		0.38
gMVP		0.36
Mutation Taster		=90/10	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: rs775086288; hg19: chr10-106034698;