rs3219218

Variant names:

• chr12-109100430-A-G
• rs3219218
• NM_080911.3:c.435+1146A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

UNG Gene-Disease associations (from GenCC):

• hyper-IgM syndrome type 5

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080911.3. 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
	UNG	NM_080911.3	MANE Select	c.435+1146A>G		intron	N/A	NP_550433.1	E5KTA5
	UNG	NM_003362.4		c.408+1146A>G		intron	N/A	NP_003353.1	P13051-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNG	ENST00000242576.7	TSL:1 MANE Select	c.435+1146A>G		intron	N/A	ENSP00000242576.3	P13051-1
	UNG	ENST00000336865.6	TSL:1	c.408+1146A>G		intron	N/A	ENSP00000337398.2	P13051-2
	UNG	ENST00000446767.2	TSL:1	n.408+1146A>G		intron	N/A	ENSP00000400287.2	Q68DM5

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

African (AFR) AF: 0.00804 AC: 334 AN: 41564

American (AMR) AF: 0.0511 AC: 780 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00230 AC: 8 AN: 3472

East Asian (EAS) AF: 0.273 AC: 1409 AN: 5170

South Asian (SAS) AF: 0.0267 AC: 129 AN: 4826

European-Finnish (FIN) AF: 0.0540 AC: 573 AN: 10604

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

European-Non Finnish (NFE) AF: 0.00212 AC: 144 AN: 68012

Other (OTH) AF: 0.0246 AC: 52 AN: 2114

Alfa AF: 0.00751 Hom.: 16

Bravo AF: 0.0240

Asia WGS AF: 0.143 AC: 494 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.7
DANN	Benign	0.48
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs3219218; hg19: chr12-109538235;