rs1805373

Variant names:

• chr3-9754824-G-A
• rs1805373
• NM_002542.6:c.686G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-9754824-G-A
• chr3-9754824-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 38 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0028837025).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0831 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002542.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OGG1	NM_002542.6	MANE Select	c.686G>A	p.Arg229Gln	missense	Exon 4 of 7	NP_002533.1	O15527-1
	OGG1	NM_016821.3		c.686G>A	p.Arg229Gln	missense	Exon 4 of 7	NP_058214.1	O15527-4
	OGG1	NM_016820.4		c.686G>A	p.Arg229Gln	missense	Exon 4 of 7	NP_058213.1	E5KPN0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OGG1	ENST00000344629.12	TSL:1 MANE Select	c.686G>A	p.Arg229Gln	missense	Exon 4 of 7	ENSP00000342851.7	O15527-1
	OGG1	ENST00000302036.12	TSL:1	c.686G>A	p.Arg229Gln	missense	Exon 4 of 7	ENSP00000306561.7	O15527-4
	OGG1	ENST00000302003.11	TSL:1	c.686G>A	p.Arg229Gln	missense	Exon 4 of 7	ENSP00000305584.7	O15527-3

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

GnomAD2 exomes AF: 0.00659 AC: 1616 AN: 245164 AF XY: 0.00470

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 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

African (AFR) AF: 0.0827 AC: 2764 AN: 33442

American (AMR) AF: 0.00536 AC: 238 AN: 44374

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26024

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39648

South Asian (SAS) AF: 0.000140 AC: 12 AN: 85620

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53284

Middle Eastern (MID) AF: 0.00347 AC: 20 AN: 5764

European-Non Finnish (NFE) AF: 0.000281 AC: 312 AN: 1111034

Other (OTH) AF: 0.00590 AC: 356 AN: 60328

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

African (AFR) AF: 0.0854 AC: 3548 AN: 41544

American (AMR) AF: 0.0102 AC: 156 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000397 AC: 27 AN: 68026

Other (OTH) AF: 0.0166 AC: 35 AN: 2114

Alfa AF: 0.00724 Hom.: 158

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 v4.9

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
MetaRNN	Benign	0.0029	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.6
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.13
Sift	Benign	0.070	T
Sift4G	Benign	0.10	T
Polyphen		0.31	B
Vest4		0.14
MVP		0.76
MPC		0.13
ClinPred		0.034	T
GERP RS		3.1
Varity_R		0.26
gMVP		0.67
Mutation Taster		=75/25	polymorphism (auto)

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

Other links and lift over

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