rs1052133

chr3-9757089-C-Gchr3-9757089-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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 (★). 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 criteria provided, single submitter 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 -14 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 criteria_provided_single_submitter, 1 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	UniProt
OGG1	NM_002542.6	c.977C>G	p.Ser326Cys	missense_variant	7/7	ENST00000344629.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OGG1	ENST00000344629.12	c.977C>G	p.Ser326Cys	missense_variant	7/7	1	NM_002542.6	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: criteria provided, single submitter

Submissions by phenotype

OGG1-related disorder Benign:1

Benign, criteria provided, single submitter

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;