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 -9 ACMG points: 0P and 9B. BP4_Strong BP6 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. 17/23 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• 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

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004373193).
• BP6: Variant 3-9751060-G-T is Benign according to our data. Variant chr3-9751060-G-T is described in Lovd as [Likely_benign].
• 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

Gnomad4 AFR exome AF: 0.000418 AC: 14 AN: 33472

Gnomad4 AMR exome AF: 0.000448 AC: 20 AN: 44666

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26130

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39694

Gnomad4 SAS exome AF: 0.00 AC: 0 AN: 86200

Gnomad4 FIN exome AF: 0.000281 AC: 15 AN: 53404

Gnomad4 NFE exome AF: 0.00282 AC: 3132 AN: 1111848

Gnomad4 Remaining exome 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

Gnomad4 AFR AF: 0.000433 AC: 0.000433296 AN: 0.000433296

Gnomad4 AMR AF: 0.000654 AC: 0.00065368 AN: 0.00065368

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.000566 AC: 0.000565718 AN: 0.000565718

Gnomad4 NFE AF: 0.00254 AC: 0.00254337 AN: 0.00254337

Gnomad4 OTH AF: 0.00189 AC: 0.00189036 AN: 0.00189036

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	0.026	.;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
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
Polyphen		0.0	.;B;.;.;B;.;.;.
Vest4		0.21
MVP		0.35
MPC		0.097
ClinPred		0.0032	T
GERP RS		-3.6
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

Publications

LitVar

Other links and lift over

dbSNP: rs17050550; hg19: chr3-9792744;