3-9756779-G-T

Variant names:

• chr3-9756779-G-T
• rs376666435
• NM_002542.6:c.911G>T

Variant summary

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

The NM_001354650.2(OGG1):​c.760G>T​(p.Gly254*) variant causes a stop gained change. 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OGG1 NM_001354650.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.87
• Publications: 2 publications found

Genes affected

OGG1 (HGNC:8125): (8-oxoguanine DNA glycosylase) This gene encodes the enzyme responsible for the excision of 8-oxoguanine, a mutagenic base byproduct which occurs as a result of exposure to reactive oxygen. The action of this enzyme includes lyase activity for chain cleavage. Alternative splicing of the C-terminal region of this gene classifies splice variants into two major groups, type 1 and type 2, depending on the last exon of the sequence. Type 1 alternative splice variants end with exon 7 and type 2 end with exon 8. All variants share the N-terminal region in common, which contains a mitochondrial targeting signal that is essential for mitochondrial localization. Many alternative splice variants for this gene have been described, but the full-length nature for every variant has not been determined. [provided by RefSeq, Aug 2008]

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_001354650.2. 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
	OGG1	NM_002542.6	MANE Select	c.911G>T	p.Arg304Leu	missense	Exon 6 of 7	NP_002533.1	O15527-1
	OGG1	NM_001354650.2		c.760G>T	p.Gly254*	stop_gained	Exon 5 of 6	NP_001341579.1	A0A9L9PXU1
	OGG1	NM_001354652.2		c.760G>T	p.Gly254*	stop_gained	Exon 5 of 7	NP_001341581.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OGG1	ENST00000344629.12	TSL:1 MANE Select	c.911G>T	p.Arg304Leu	missense	Exon 6 of 7	ENSP00000342851.7	O15527-1
	OGG1	ENST00000302036.12	TSL:1	c.911G>T	p.Arg304Leu	missense	Exon 6 of 7	ENSP00000306561.7	O15527-4
	OGG1	ENST00000302003.11	TSL:1	c.911G>T	p.Arg304Leu	missense	Exon 6 of 7	ENSP00000305584.7	O15527-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

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	Uncertain	0.46
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.034	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.52	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		6.9
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Uncertain	0.36
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.025	D
Polyphen		1.0	D
Vest4		0.80
MutPred		0.61		Loss of MoRF binding (P = 0.0109)
MVP		0.85
MPC		0.34
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.78
gMVP		0.85
Mutation Taster		=29/71	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.29		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.29		Position offset: -12

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs376666435; hg19: chr3-9798463;