Variant chr3-9751060-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000344629.12(OGG1):c.253G>A(p.Ala85Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A85S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.030109555).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OGG1	NM_002542.6 linkuse as main transcript	c.253G>A	p.Ala85Thr	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>A	p.Ala85Thr	missense_variant	2/7	1	NM_002542.6	ENSP00000342851	P1	O15527-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250510

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135410

show subpopulations

Gnomad AFR exome

AF:

0.0000619

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152274

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.51

CADD

Benign

5.3

DANN

Benign

0.71

DEOGEN2

Benign

0.026

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

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.54

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

M_CAP

Benign

0.011

MetaRNN

Benign

0.030

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.70

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

-0.11

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

REVEL

Benign

0.018

Sift

Benign

0.34

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

Sift4G

Benign

0.53

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

Polyphen

0.0030, 0.0040

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

Vest4

0.056

MutPred

0.36

Loss of glycosylation at P90 (P = 0.0225);Loss of glycosylation at P90 (P = 0.0225);Loss of glycosylation at P90 (P = 0.0225);Loss of glycosylation at P90 (P = 0.0225);Loss of glycosylation at P90 (P = 0.0225);Loss of glycosylation at P90 (P = 0.0225);Loss of glycosylation at P90 (P = 0.0225);Loss of glycosylation at P90 (P = 0.0225);

MVP

0.37

MPC

0.096

ClinPred

0.071

GERP RS

-3.6

Varity_R

0.052

gMVP

0.43

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