rs1805373

Positions:

• chr3-9754824-G-A
• chr3-9754824-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_002542.6(OGG1):​c.686G>A​(p.Arg229Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00464 in 1,611,808 control chromosomes in the GnomAD database, including 269 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.025 (147 hom., cov: 33)
  • Exomes 𝑓: 0.0025 (122 hom.)
• Consequence: OGG1 NM_002542.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.59

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0028837025).
• BP6: Variant 3-9754824-G-A is Benign according to our data. Variant chr3-9754824-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OGG1	NM_002542.6	c.686G>A	p.Arg229Gln	missense_variant	4/7	ENST00000344629.12	NP_002533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OGG1	ENST00000344629.12	c.686G>A	p.Arg229Gln	missense_variant	4/7	1	NM_002542.6	ENSP00000342851	P1

Frequencies

GnomAD3 genomes AF: 0.0247 AC: 3764 AN: 152172 Hom.: 147 Cov.: 33

Gnomad AFR AF: 0.0855

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0102

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.0167

GnomAD3 exomes AF: 0.00659 AC: 1616 AN: 245164 Hom.: 53 AF XY: 0.00470 AC XY: 623 AN XY: 132618

Gnomad AFR exome AF: 0.0898

Gnomad AMR exome AF: 0.00482

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000550

Gnomad SAS exome AF: 0.000134

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000297

Gnomad OTH exome AF: 0.00452

GnomAD4 exome AF: 0.00254 AC: 3703 AN: 1459518 Hom.: 122 Cov.: 32 AF XY: 0.00213 AC XY: 1547 AN XY: 725824

Gnomad4 AFR exome AF: 0.0827

Gnomad4 AMR exome AF: 0.00536

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000140

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000281

Gnomad4 OTH exome AF: 0.00590

GnomAD4 genome AF: 0.0248 AC: 3771 AN: 152290 Hom.: 147 Cov.: 33 AF XY: 0.0245 AC XY: 1826 AN XY: 74476

Gnomad4 AFR AF: 0.0854

Gnomad4 AMR AF: 0.0102

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000397

Gnomad4 OTH AF: 0.0166

Alfa AF: 0.00398 Hom.: 31

Bravo AF: 0.0276

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0872 AC: 384

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00819 AC: 994

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	.;T;.;.;.;.;.
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.79	T;T;T;T;T;T;T
MetaRNN	Benign	0.0029	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;L;L;L;L;L;L
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.7	D;D;D;D;D;D;D
REVEL	Benign	0.13
Sift	Benign	0.070	T;D;D;D;D;D;D
Sift4G	Benign	0.10	T;T;D;D;T;T;T
Polyphen		0.31, 0.93	.;B;.;.;P;.;.
Vest4		0.14
MVP		0.76
MPC		0.13
ClinPred		0.034	T
GERP RS		3.1
Varity_R		0.26
gMVP		0.67

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

Other links and lift over

dbSNP: rs1805373; hg19: chr3-9796508; COSMIC: COSV56539691; COSMIC: COSV56539691;