chr3-9756791-G-A

Position:

chr3-9756791-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP3BP4_StrongBP6_ModerateBS2

The NM_002542.6(OGG1):c.923G>A(p.Gly308Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00487 in 1,614,070 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0036 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0050 ( 26 hom. )

Consequence

OGG1
NM_002542.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 8.63

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 8: AlphaMissense, BayesDel_noAF, Cadd, Eigen, MutationAssessor, phyloP100way_vertebrate, PROVEAN, REVEL [when max_spliceai, FATHMM_MKL, M_CAP, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.038028896).

BP6

Variant 3-9756791-G-A is Benign according to our data. Variant chr3-9756791-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2653500.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-9756791-G-A is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAdExome4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OGG1	NM_002542.6 linkuse as main transcript	c.923G>A	p.Gly308Glu	missense_variant	6/7	ENST00000344629.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OGG1	ENST00000344629.12 linkuse as main transcript	c.923G>A	p.Gly308Glu	missense_variant	6/7	1	NM_002542.6	P1	O15527-1

Frequencies

GnomAD3 genomes

AF:

0.00359

AC:

546

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00485

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00569

Gnomad OTH

AF:

0.00623

GnomAD3 exomes

AF:

0.00387

AC:

972

AN:

251476

Hom.:

AF XY:

0.00394

AC XY:

536

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.000923

Gnomad AMR exome

AF:

0.00356

Gnomad ASJ exome

AF:

0.00288

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000457

Gnomad FIN exome

AF:

0.00102

Gnomad NFE exome

AF:

0.00648

Gnomad OTH exome

AF:

0.00521

GnomAD4 exome

AF:

0.00501

AC:

7323

AN:

1461838

Hom.:

Cov.:

AF XY:

0.00503

AC XY:

3655

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.000866

Gnomad4 AMR exome

AF:

0.00400

Gnomad4 ASJ exome

AF:

0.00295

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000568

Gnomad4 FIN exome

AF:

0.00105

Gnomad4 NFE exome

AF:

0.00599

Gnomad4 OTH exome

AF:

0.00434

GnomAD4 genome

AF:

0.00358

AC:

545

AN:

152232

Hom.:

Cov.:

AF XY:

0.00318

AC XY:

237

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.000963

Gnomad4 AMR

AF:

0.00484

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00160

Gnomad4 NFE

AF:

0.00568

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00565

Hom.:

Bravo

AF:

0.00392

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00558

AC:

ExAC

AF:

0.00412

AC:

500

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00660

EpiControl

AF:

0.00610

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

OGG1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 13, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

OGG1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.79

BayesDel_addAF

Uncertain

0.034

BayesDel_noAF

Pathogenic

0.28

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.46

.;T;.;.;.;.

Eigen

Pathogenic

0.95

Eigen_PC

Pathogenic

0.90

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

D;D;D;D;D;D

M_CAP

Benign

0.038

MetaRNN

Benign

0.038

T;T;T;T;T;T

MetaSVM

Uncertain

-0.23

MutationAssessor

Pathogenic

3.6

H;H;H;H;H;H

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.59

PROVEAN

Pathogenic

-7.3

D;D;D;D;D;D

REVEL

Pathogenic

0.76

Sift

Uncertain

0.0050

D;D;D;D;D;D

Sift4G

Uncertain

0.0020

D;D;D;D;D;D

Polyphen

1.0

D;D;.;D;.;.

Vest4

0.95

MVP

0.92

MPC

0.58

ClinPred

0.086

GERP RS

5.4

Varity_R

0.98

gMVP

0.95

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over