chr10-104275276-A-T

Variant names:

• chr10-104275276-A-T
• rs771838005
• NM_183239.2:c.85A>T

Variant summary

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

The NM_183239.2(GSTO2):​c.85A>T​(p.Met29Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. M29V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GSTO2 NM_183239.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.21
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.85A>T	p.Met29Leu	missense	Exon 3 of 7	NP_899062.1	Q9H4Y5-1
	GSTO2	NM_001191013.2		c.85A>T	p.Met29Leu	missense	Exon 3 of 6	NP_001177942.1	Q9H4Y5-2
	GSTO2	NM_001191014.2		c.1A>T	p.Met1?	initiator_codon	Exon 1 of 5	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.85A>T	p.Met29Leu	missense	Exon 3 of 7	ENSP00000345023.1	Q9H4Y5-1
	GSTO2	ENST00000369707.2	TSL:1	c.1A>T	p.Met1?	initiator_codon	Exon 1 of 5	ENSP00000358721.1	Q9H4Y5-3
	GSTO2	ENST00000912037.1		c.85A>T	p.Met29Leu	missense	Exon 3 of 7	ENSP00000582096.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251368 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	28
DANN	Uncertain	0.98
DEOGEN2	Benign	0.14	T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		6.2
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.32
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.029	D
Polyphen		1.0	D
Vest4		0.61
MutPred		0.62		Gain of catalytic residue at M29 (P = 0.0083)
MVP		0.52
MPC		0.33
ClinPred		0.99	D
GERP RS		5.6
PromoterAI		-0.013	Neutral
Varity_R		0.94
gMVP		0.29
Mutation Taster		=18/182	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs771838005; hg19: chr10-106035034;