chr3-9757089-C-T

Variant names:

• chr3-9757089-C-T
• rs1052133
• NM_002542.6:c.977C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016820.4(OGG1):​c.994C>T​(p.Pro332Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P332A) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OGG1 NM_016820.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730
• Publications: 783 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16903555).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016820.4. 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.977C>T	p.Ser326Phe	missense	Exon 7 of 7	NP_002533.1
	OGG1	NM_016820.4		c.994C>T	p.Pro332Ser	missense	Exon 7 of 7	NP_058213.1
	OGG1	NM_001354649.2		c.644C>T	p.Ser215Phe	missense	Exon 5 of 5	NP_001341578.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OGG1	ENST00000344629.12	TSL:1 MANE Select	c.977C>T	p.Ser326Phe	missense	Exon 7 of 7	ENSP00000342851.7
	OGG1	ENST00000302003.11	TSL:1	c.994C>T	p.Pro332Ser	missense	Exon 7 of 7	ENSP00000305584.7
	OGG1	ENST00000416333.1	TSL:1	c.292C>T	p.Pro98Ser	missense	Exon 4 of 4	ENSP00000402713.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.76
DANN	Benign	0.71
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.073
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.050	N
REVEL	Benign	0.13
Sift	Benign	0.39	T
Sift4G	Benign	0.19	T
Polyphen		0.0070	B
Vest4		0.083
MutPred		0.70		Gain of MoRF binding (P = 0.0501)
MVP		0.42
ClinPred		0.037	T
GERP RS		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.027
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1052133; hg19: chr3-9798773;