12-109098052-T-G

Variant names:

• chr12-109098052-T-G
• rs1018783
• NM_080911.3:c.132+241T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_080911.3(UNG):​c.132+241T>G variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: UNG NM_080911.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.503
• Publications: 7 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNG	NM_080911.3	c.132+241T>G		intron_variant	Intron 1 of 6	ENST00000242576.7	NP_550433.1
UNG	NM_003362.4	c.-275T>G		upstream_gene_variant			NP_003353.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNG	ENST00000242576.7	c.132+241T>G		intron_variant	Intron 1 of 6	1	NM_080911.3	ENSP00000242576.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1217384 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 586962

African (AFR) AF: 0.00 AC: 0 AN: 25700

American (AMR) AF: 0.00 AC: 0 AN: 16774

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17558

East Asian (EAS) AF: 0.00 AC: 0 AN: 31816

South Asian (SAS) AF: 0.00 AC: 0 AN: 53100

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3400

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 989966

Other (OTH) AF: 0.00 AC: 0 AN: 50490

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 495

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	10
DANN	Benign	0.59
PhyloP100		0.50
PromoterAI		0.011	Neutral

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: rs1018783; hg19: chr12-109535857;