rs1052133

Positions:

• chr3-9757089-C-G
• chr3-9757089-C-T

Variant summary

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

The NM_002542.6(OGG1):​c.977C>G​(p.Ser326Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 1,614,026 control chromosomes in the GnomAD database, including 50,216 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.22 (4185 hom., cov: 32)
  • Exomes 𝑓: 0.24 (46031 hom.)
• Consequence: OGG1 NM_002542.6 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.0730

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=1.0405932E-4).
• BP6: Variant 3-9757089-C-G is Benign according to our data. Variant chr3-9757089-C-G is described in ClinVar as [Benign]. Clinvar id is 3059470.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OGG1	NM_002542.6	c.977C>G	p.Ser326Cys	missense_variant	7/7	ENST00000344629.12	NP_002533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OGG1	ENST00000344629.12	c.977C>G	p.Ser326Cys	missense_variant	7/7	1	NM_002542.6	ENSP00000342851	P1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33640 AN: 152114 Hom.: 4196 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.227

GnomAD3 exomes AF: 0.274 AC: 68570 AN: 250506 Hom.: 11017 AF XY: 0.270 AC XY: 36667 AN XY: 135562

Gnomad AFR exome AF: 0.164

Gnomad AMR exome AF: 0.358

Gnomad ASJ exome AF: 0.215

Gnomad EAS exome AF: 0.596

Gnomad SAS exome AF: 0.318

Gnomad FIN exome AF: 0.184

Gnomad NFE exome AF: 0.223

Gnomad OTH exome AF: 0.250

GnomAD4 exome AF: 0.243 AC: 355035 AN: 1461794 Hom.: 46031 Cov.: 38 AF XY: 0.244 AC XY: 177609 AN XY: 727190

Gnomad4 AFR exome AF: 0.161

Gnomad4 AMR exome AF: 0.342

Gnomad4 ASJ exome AF: 0.208

Gnomad4 EAS exome AF: 0.531

Gnomad4 SAS exome AF: 0.317

Gnomad4 FIN exome AF: 0.184

Gnomad4 NFE exome AF: 0.228

Gnomad4 OTH exome AF: 0.251

GnomAD4 genome AF: 0.221 AC: 33628 AN: 152232 Hom.: 4185 Cov.: 32 AF XY: 0.220 AC XY: 16365 AN XY: 74410

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.197

Gnomad4 EAS AF: 0.572

Gnomad4 SAS AF: 0.330

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.224

Alfa AF: 0.221 Hom.: 1284

Bravo AF: 0.228

TwinsUK AF: 0.232 AC: 859

ALSPAC AF: 0.225 AC: 868

ESP6500AA AF: 0.174 AC: 767

ESP6500EA AF: 0.230 AC: 1979

ExAC AF: 0.271 AC: 32872

Asia WGS AF: 0.386 AC: 1340 AN: 3478

EpiCase AF: 0.230

EpiControl AF: 0.229

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

OGG1-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	8.3
DANN	Benign	0.75
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.33	T
MetaRNN	Benign	0.00010	T
MetaSVM	Benign	-0.90	T
MutationTaster	Benign	1.0	P;P;P;P;P;P;P;P
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.099
Sift	Benign	0.49	T
Sift4G	Benign	0.17	T
Polyphen		0.10	B
Vest4		0.080
ClinPred		0.0072	T
GERP RS		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1052133; hg19: chr3-9798773; COSMIC: COSV56537677; COSMIC: COSV56537677;