3-9756779-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OGG1	NM_002542.6	c.911G>T	p.Arg304Leu	missense_variant	Exon 6 of 7	ENST00000344629.12	NP_002533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OGG1	ENST00000344629.12	c.911G>T	p.Arg304Leu	missense_variant	Exon 6 of 7	1	NM_002542.6	ENSP00000342851.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;D;D;D;D;D
M_CAP	Benign	0.034	D
MetaRNN	Pathogenic	0.82	D;D;D;D;D;D
MetaSVM	Benign	-0.52	T
MutationAssessor	Pathogenic	3.1	M;M;M;M;M;M
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-5.5	D;D;D;D;D;D
REVEL	Uncertain	0.36
Sift	Uncertain	0.018	D;D;T;D;D;D
Sift4G	Uncertain	0.025	D;D;D;D;D;D
Polyphen		1.0	D;P;.;D;.;.
Vest4		0.80
MutPred		0.61		Loss of MoRF binding (P = 0.0109);Loss of MoRF binding (P = 0.0109);Loss of MoRF binding (P = 0.0109);Loss of MoRF binding (P = 0.0109);Loss of MoRF binding (P = 0.0109);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

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

Publications

LitVar

Other links and lift over

dbSNP: rs376666435; hg19: chr3-9798463;