NM_002542.6:c.995C>G

Variant names:

• chr3-9757107-C-G
• NM_002542.6:c.995C>G
• OGG1 p.Pro332Arg

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002542.6(OGG1):​c.995C>G​(p.Pro332Arg) 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. 15/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OGG1 NM_002542.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42
• Publications: 0 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]

CAMK1 (HGNC:1459): (calcium/calmodulin dependent protein kinase I) Calcium/calmodulin-dependent protein kinase I is expressed in many tissues and is a component of a calmodulin-dependent protein kinase cascade. Calcium/calmodulin directly activates calcium/calmodulin-dependent protein kinase I by binding to the enzyme and indirectly promotes the phosphorylation and synergistic activation of the enzyme by calcium/calmodulin-dependent protein kinase I kinase. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28304768).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002542.6. 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.995C>G	p.Pro332Arg	missense	Exon 7 of 7	NP_002533.1	O15527-1
	OGG1	NM_016820.4		c.1012C>G	p.His338Asp	missense	Exon 7 of 7	NP_058213.1	E5KPN0
	OGG1	NM_001354649.2		c.662C>G	p.Pro221Arg	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.995C>G	p.Pro332Arg	missense	Exon 7 of 7	ENSP00000342851.7	O15527-1
	OGG1	ENST00000302003.11	TSL:1	c.1012C>G	p.His338Asp	missense	Exon 7 of 7	ENSP00000305584.7	O15527-3
	OGG1	ENST00000416333.1	TSL:1	c.310C>G	p.His104Asp	missense	Exon 4 of 4	ENSP00000402713.1	H7C1V7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	20
DANN	Uncertain	0.98
Eigen	Benign	-0.051
Eigen_PC	Benign	0.049
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.94	T
PhyloP100		1.4
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.16
Sift	Benign	0.15	T
Sift4G	Benign	0.29	T
Varity_R		0.052
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-9798791;