3-9751060-G-T

Variant names:

• chr3-9751060-G-T
• rs17050550
• NM_002542.6:c.253G>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_002542.6(OGG1):​c.253G>T​(p.Ala85Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00216 in 1,613,834 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 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 0.0014 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (6 hom.)
• Consequence: OGG1 NM_002542.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.836
• Publications: 19 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004373193).
• BS2: High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OGG1	NM_002542.6	c.253G>T	p.Ala85Ser	missense_variant	Exon 2 of 7	ENST00000344629.12	NP_002533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OGG1	ENST00000344629.12	c.253G>T	p.Ala85Ser	missense_variant	Exon 2 of 7	1	NM_002542.6	ENSP00000342851.7

Frequencies

GnomAD3 genomes AF: 0.00139 AC: 211 AN: 152156 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000435

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000566

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00254

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00143 AC: 358 AN: 250510 AF XY: 0.00136

Gnomad AFR exome AF: 0.000557

Gnomad AMR exome AF: 0.000377

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000371

Gnomad NFE exome AF: 0.00283

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00224 AC: 3276 AN: 1461560 Hom.: 6 Cov.: 31 AF XY: 0.00217 AC XY: 1578 AN XY: 727054

African (AFR) AF: 0.000418 AC: 14 AN: 33472

American (AMR) AF: 0.000448 AC: 20 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86200

European-Finnish (FIN) AF: 0.000281 AC: 15 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00282 AC: 3132 AN: 1111848

Other (OTH) AF: 0.00157 AC: 95 AN: 60378

GnomAD4 genome AF: 0.00139 AC: 211 AN: 152274 Hom.: 1 Cov.: 32 AF XY: 0.00117 AC XY: 87 AN XY: 74464

African (AFR) AF: 0.000433 AC: 18 AN: 41542

American (AMR) AF: 0.000654 AC: 10 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.000566 AC: 6 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00254 AC: 173 AN: 68020

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.00203 Hom.: 0

Bravo AF: 0.00151

TwinsUK AF: 0.00351 AC: 13

ALSPAC AF: 0.00208 AC: 8

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00279 AC: 24

ExAC AF: 0.00147 AC: 179

EpiCase AF: 0.00202

EpiControl AF: 0.00250

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	2.7
DANN	Benign	0.61
DEOGEN2	Benign	0.0	.;T;.;.;.;.;.;.
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.71	T;T;T;T;T;T;T;T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.0044	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.56	N;N;N;N;N;N;N;N
PhyloP100		0.84
PrimateAI	Benign	0.22	T
PROVEAN	Benign	0.27	N;N;N;N;N;N;N;N
REVEL	Benign	0.037
Sift	Benign	0.48	T;T;T;T;T;T;T;T
Sift4G	Benign	0.60	T;T;T;T;T;T;T;T
Vest4		0.21
ClinPred		0.0032	T
GERP RS		-3.6
PromoterAI		0.0058	Neutral
Varity_R		0.072
gMVP		0.44
Mutation Taster		=99/1	polymorphism

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: rs17050550; hg19: chr3-9792744;