12-109109255-A-G

Variant names:

• chr12-109109255-A-G
• rs246079
• NM_080911.3:c.802-574A>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.802-574A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 151,910 control chromosomes in the GnomAD database, including 23,744 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 0.54 (23744 hom., cov: 31)
• Consequence: UNG NM_080911.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58
• Publications: 24 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.704 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNG	NM_080911.3	MANE Select	c.802-574A>G		intron	N/A	NP_550433.1
	UNG	NM_003362.4		c.775-574A>G		intron	N/A	NP_003353.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNG	ENST00000242576.7	TSL:1 MANE Select	c.802-574A>G		intron	N/A	ENSP00000242576.3
	UNG	ENST00000336865.6	TSL:1	c.775-574A>G		intron	N/A	ENSP00000337398.2
	UNG	ENST00000446767.2	TSL:1	n.*251-574A>G		intron	N/A	ENSP00000400287.2

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82662 AN: 151792 Hom.: 23696 Cov.: 31

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.721

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.532

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

GnomAD4 genome AF: 0.545 AC: 82771 AN: 151910 Hom.: 23744 Cov.: 31 AF XY: 0.548 AC XY: 40660 AN XY: 74218

African (AFR) AF: 0.711 AC: 29422 AN: 41396

American (AMR) AF: 0.606 AC: 9252 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1608 AN: 3464

East Asian (EAS) AF: 0.721 AC: 3714 AN: 5150

South Asian (SAS) AF: 0.509 AC: 2452 AN: 4816

European-Finnish (FIN) AF: 0.495 AC: 5213 AN: 10538

Middle Eastern (MID) AF: 0.390 AC: 114 AN: 292

European-Non Finnish (NFE) AF: 0.435 AC: 29572 AN: 67968

Other (OTH) AF: 0.534 AC: 1126 AN: 2110

Alfa AF: 0.445 Hom.: 5020

Bravo AF: 0.559

Asia WGS AF: 0.625 AC: 2174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.53
DANN	Benign	0.49
PhyloP100		-1.6
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: rs246079; hg19: chr12-109547060;