Variant 3-9751060-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The ENST00000344629.12(OGG1):c.253G>T(p.Ala85Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00216 in 1,613,834 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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 0.0014 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 6 hom. )

Consequence

OGG1
ENST00000344629.12 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.836

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004373193).

BP6

Variant 3-9751060-G-T is Benign according to our data. Variant chr3-9751060-G-T is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OGG1	NM_002542.6 linkuse as main transcript	c.253G>T	p.Ala85Ser	missense_variant	2/7	ENST00000344629.12	NP_002533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OGG1	ENST00000344629.12 linkuse as main transcript	c.253G>T	p.Ala85Ser	missense_variant	2/7	1	NM_002542.6	ENSP00000342851	P1	O15527-1

Frequencies

GnomAD3 genomes

AF:

0.00139

AC:

211

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000435

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000566

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00254

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00143

AC:

358

AN:

250510

Hom.:

AF XY:

0.00136

AC XY:

184

AN XY:

135410

show subpopulations

Gnomad AFR exome

AF:

0.000557

Gnomad AMR exome

AF:

0.000377

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000371

Gnomad NFE exome

AF:

0.00283

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00224

AC:

3276

AN:

1461560

Hom.:

Cov.:

AF XY:

0.00217

AC XY:

1578

AN XY:

727054

show subpopulations

Gnomad4 AFR exome

AF:

0.000418

Gnomad4 AMR exome

AF:

0.000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000281

Gnomad4 NFE exome

AF:

0.00282

Gnomad4 OTH exome

AF:

0.00157

GnomAD4 genome

AF:

0.00139

AC:

211

AN:

152274

Hom.:

Cov.:

AF XY:

0.00117

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000566

Gnomad4 NFE

AF:

0.00254

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00219

Hom.:

Bravo

AF:

0.00151

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00279

AC:

ExAC

AF:

0.00147

AC:

179

EpiCase

AF:

0.00202

EpiControl

AF:

0.00250

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.54

CADD

Benign

2.7

DANN

Benign

0.61

DEOGEN2

Benign

0.026

.;T;.;.;.;.;.;.

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.71

T;T;T;T;T;T;T;T

M_CAP

Benign

0.0070

MetaRNN

Benign

0.0044

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.56

N;N;N;N;N;N;N;N

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

0.27

N;N;N;N;N;N;N;N

REVEL

Benign

0.037

Sift

Benign

0.48

T;T;T;T;T;T;T;T

Sift4G

Benign

0.60

T;T;T;T;T;T;T;T

Polyphen

0.0

.;B;.;.;B;.;.;.

Vest4

0.21

MVP

0.35

MPC

0.097

ClinPred

0.0032

GERP RS

-3.6

Varity_R

0.072

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over