NM_004832.3:c.488C>T

Variant names:

• chr10-104266106-C-T
• rs116993524
• NM_004832.3:c.488C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_004832.3(GSTO1):​c.488C>T​(p.Thr163Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00306 in 1,600,274 control chromosomes in the GnomAD database, including 12 homozygotes. 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0032 (11 hom.)
• Consequence: GSTO1 NM_004832.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.510
• Publications: 7 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011708558).
• BP6: Variant 10-104266106-C-T is Benign according to our data. Variant chr10-104266106-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 715814.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 11 AR gene

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.488C>T	p.Thr163Ile	missense	Exon 5 of 6	NP_004823.1	P78417-1
	GSTO1	NM_001191003.2		c.404C>T	p.Thr135Ile	missense	Exon 5 of 6	NP_001177932.1	P78417-3
	GSTO1	NM_001191002.2		c.389C>T	p.Thr130Ile	missense	Exon 4 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.488C>T	p.Thr163Ile	missense	Exon 5 of 6	ENSP00000358727.5	P78417-1
	GSTO1	ENST00000539281.5	TSL:5	c.404C>T	p.Thr135Ile	missense	Exon 5 of 6	ENSP00000441488.1	P78417-3
	GSTO1	ENST00000369710.8	TSL:2	c.389C>T	p.Thr130Ile	missense	Exon 4 of 5	ENSP00000358724.4	P78417-2

Frequencies

GnomAD3 genomes AF: 0.00166 AC: 252 AN: 152178 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000754

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00309

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00201 AC: 504 AN: 251360 AF XY: 0.00189

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000405

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00171

Gnomad NFE exome AF: 0.00383

Gnomad OTH exome AF: 0.00228

GnomAD4 exome AF: 0.00320 AC: 4638 AN: 1447978 Hom.: 11 Cov.: 26 AF XY: 0.00304 AC XY: 2194 AN XY: 721220

African (AFR) AF: 0.000391 AC: 13 AN: 33208

American (AMR) AF: 0.000559 AC: 25 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26038

East Asian (EAS) AF: 0.00 AC: 0 AN: 39618

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 85966

European-Finnish (FIN) AF: 0.00156 AC: 83 AN: 53376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 0.00398 AC: 4379 AN: 1099434

Other (OTH) AF: 0.00229 AC: 137 AN: 59908

GnomAD4 genome AF: 0.00165 AC: 252 AN: 152296 Hom.: 1 Cov.: 33 AF XY: 0.00161 AC XY: 120 AN XY: 74478

African (AFR) AF: 0.000385 AC: 16 AN: 41556

American (AMR) AF: 0.00111 AC: 17 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.000754 AC: 8 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00309 AC: 210 AN: 68032

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.00284 Hom.: 1

Bravo AF: 0.00174

TwinsUK AF: 0.00458 AC: 17

ALSPAC AF: 0.00285 AC: 11

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00256 AC: 22

ExAC AF: 0.00226 AC: 274

EpiCase AF: 0.00207

EpiControl AF: 0.00202

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	8.2
DANN	Benign	0.93
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		0.51
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.060
Sift	Benign	0.19	T
Sift4G	Benign	0.20	T
Polyphen		0.0050	B
Vest4		0.29
MVP		0.40
MPC		0.18
ClinPred		0.024	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.33
gMVP		0.24
Mutation Taster		=85/15	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: rs116993524; hg19: chr10-106025864; COSMIC: COSV58539553; COSMIC: COSV58539553;