3-9750423-G-A

Position:

chr3-9750423-G-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_002542.6(OGG1):c.137G>A(p.Arg46Gln) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00333 in 1,613,860 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0023 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0034 ( 8 hom. )

Consequence

OGG1
NM_002542.6 missense, splice_region

Scores

Splicing: ADA: 0.9997

Clinical Significance

Uncertain significance criteria provided, single submitter P:1U:3

Conservation

PhyloP100: 6.30

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 Likely_benign. Variant got -3 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 7: BayesDel_noAF, Cadd, Dann, dbscSNV1_ADA, dbscSNV1_RF, Eigen, MutationAssessor [when FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]

BS2

High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OGG1	NM_002542.6 linkuse as main transcript	c.137G>A	p.Arg46Gln	missense_variant, splice_region_variant	1/7	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.137G>A	p.Arg46Gln	missense_variant, splice_region_variant	1/7	1	NM_002542.6	ENSP00000342851	P1	O15527-1

Frequencies

GnomAD3 genomes

AF:

0.00225

AC:

343

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000941

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.00223

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00367

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00221

AC:

553

AN:

249786

Hom.:

AF XY:

0.00223

AC XY:

301

AN XY:

135194

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.00188

Gnomad ASJ exome

AF:

0.000794

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000425

Gnomad FIN exome

AF:

0.000561

Gnomad NFE exome

AF:

0.00383

Gnomad OTH exome

AF:

0.00229

GnomAD4 exome

AF:

0.00344

AC:

5035

AN:

1461558

Hom.:

Cov.:

AF XY:

0.00332

AC XY:

2412

AN XY:

727114

show subpopulations

Gnomad4 AFR exome

AF:

0.000657

Gnomad4 AMR exome

AF:

0.00221

Gnomad4 ASJ exome

AF:

0.000689

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000522

Gnomad4 FIN exome

AF:

0.000584

Gnomad4 NFE exome

AF:

0.00418

Gnomad4 OTH exome

AF:

0.00288

GnomAD4 genome

AF:

0.00225

AC:

343

AN:

152302

Hom.:

Cov.:

AF XY:

0.00201

AC XY:

150

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000938

Gnomad4 AMR

AF:

0.00222

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00368

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00309

Hom.:

Bravo

AF:

0.00254

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00302

AC:

ExAC

AF:

0.00205

AC:

249

EpiCase

AF:

0.00398

EpiControl

AF:

0.00332

ClinVar

Significance: Uncertain significance

Submissions summary: Pathogenic:1Uncertain:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:3

Uncertain significance, criteria provided, single submitter	clinical testing	AiLife Diagnostics, AiLife Diagnostics	Jul 31, 2021	- -
Uncertain significance, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Uncertain significance, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -

Clear cell carcinoma of kidney

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 01, 2000

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Uncertain

0.034

BayesDel_noAF

Pathogenic

0.28

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.33

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

Eigen

Pathogenic

0.88

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.97

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

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.035

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

MetaSVM

Uncertain

0.27

MutationAssessor

Pathogenic

3.9

H;H;H;H;H;H;H;H

MutationTaster

Benign

1.0

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

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-3.3

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

REVEL

Uncertain

0.59

Sift

Uncertain

0.0010

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

Sift4G

Uncertain

0.0050

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

Polyphen

1.0

.;D;.;.;D;.;.;.

Vest4

0.76

MVP

0.84

MPC

0.55

ClinPred

0.11

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.95

gMVP

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.99

SpliceAI score (max)

0.39

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.39

Position offset: 0

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