rs3219218

Positions:

• chr12-109100430-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080911.3(UNG):​c.435+1146A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0225 in 152,226 control chromosomes in the GnomAD database, including 250 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.023 (250 hom., cov: 32)
• Consequence: UNG NM_080911.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18

Genes affected

UNG (HGNC:12572): (uracil DNA glycosylase) This gene encodes one of several uracil-DNA glycosylases. One important function of uracil-DNA glycosylases is to prevent mutagenesis by eliminating uracil from DNA molecules by cleaving the N-glycosylic bond and initiating the base-excision repair (BER) pathway. Uracil bases occur from cytosine deamination or misincorporation of dUMP residues. Alternative promoter usage and splicing of this gene leads to two different isoforms: the mitochondrial UNG1 and the nuclear UNG2. The UNG2 term was used as a previous symbol for the CCNO gene (GeneID 10309), which has been confused with this gene, in the literature and some databases. [provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UNG	NM_080911.3	c.435+1146A>G		intron_variant		ENST00000242576.7	NP_550433.1
UNG	NM_003362.4	c.408+1146A>G		intron_variant			NP_003353.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UNG	ENST00000242576.7	c.435+1146A>G		intron_variant		1	NM_080911.3	ENSP00000242576	P1

Frequencies

GnomAD3 genomes AF: 0.0225 AC: 3422 AN: 152108 Hom.: 248 Cov.: 32

Gnomad AFR AF: 0.00804

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0505

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.0273

Gnomad FIN AF: 0.0540

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00212

Gnomad OTH AF: 0.0234

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0225 AC: 3429 AN: 152226 Hom.: 250 Cov.: 32 AF XY: 0.0262 AC XY: 1954 AN XY: 74438

Gnomad4 AFR AF: 0.00804

Gnomad4 AMR AF: 0.0511

Gnomad4 ASJ AF: 0.00230

Gnomad4 EAS AF: 0.273

Gnomad4 SAS AF: 0.0267

Gnomad4 FIN AF: 0.0540

Gnomad4 NFE AF: 0.00212

Gnomad4 OTH AF: 0.0246

Alfa AF: 0.00898 Hom.: 13

Bravo AF: 0.0240

Asia WGS AF: 0.143 AC: 494 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.7
DANN	Benign	0.48

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: rs3219218; hg19: chr12-109538235;