Variant 3-9756586-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2

The NM_002542.6(OGG1):c.863C>T(p.Ala288Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00194 in 1,614,112 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 3 hom. )

Consequence

OGG1
NM_002542.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.46

Variant links:

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]

OGG1 links:

OGG1 (HGNC:):

OGG1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP6

Variant 3-9756586-C-T is Benign according to our data. Variant chr3-9756586-C-T is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OGG1	NM_002542.6 linkuse as main transcript	c.863C>T	p.Ala288Val	missense_variant	5/7	ENST00000344629.12	NP_002533.1	O15527-1E5KPN1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OGG1	ENST00000344629.12 linkuse as main transcript	c.863C>T	p.Ala288Val	missense_variant	5/7	1	NM_002542.6	ENSP00000342851.7		O15527-1

Frequencies

GnomAD3 genomes

AF:

0.00147

AC:

223

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00210

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00171

AC:

430

AN:

251380

Hom.:

AF XY:

0.00162

AC XY:

220

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.00171

Gnomad ASJ exome

AF:

0.00357

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.000463

Gnomad NFE exome

AF:

0.00254

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00199

AC:

2916

AN:

1461852

Hom.:

Cov.:

AF XY:

0.00190

AC XY:

1385

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.000538

Gnomad4 AMR exome

AF:

0.00168

Gnomad4 ASJ exome

AF:

0.00425

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000243

Gnomad4 FIN exome

AF:

0.000506

Gnomad4 NFE exome

AF:

0.00230

Gnomad4 OTH exome

AF:

0.00179

GnomAD4 genome

AF:

0.00146

AC:

223

AN:

152260

Hom.:

Cov.:

AF XY:

0.00146

AC XY:

109

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.000674

Gnomad4 AMR

AF:

0.00177

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00210

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00226

Hom.:

Bravo

AF:

0.00173

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00233

AC:

ExAC

AF:

0.00161

AC:

196

EpiCase

AF:

0.00202

EpiControl

AF:

0.00196

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

.;T;.;.;.;.

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.85

T;T;T;T;T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.0092

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;L;L;L;L;L

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.1

N;N;N;N;N;N

REVEL

Benign

0.060

Sift

Benign

0.50

T;T;T;T;T;T

Sift4G

Benign

0.33

T;T;T;T;T;T

Polyphen

0.85

P;B;.;B;.;.

Vest4

0.16

MVP

0.74

MPC

0.10

ClinPred

0.016

GERP RS

3.0

Varity_R

0.12

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.56

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.56

Position offset: -2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over