12-109109870-G-C

Variant names:

• chr12-109109870-G-C
• NM_080911.3:c.843G>C
• UNG p.Leu281Phe

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_080911.3(UNG):​c.843G>C​(p.Leu281Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: UNG NM_080911.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.135
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.843G>C	p.Leu281Phe	missense	Exon 7 of 7	NP_550433.1	E5KTA5
	UNG	NM_003362.4		c.816G>C	p.Leu272Phe	missense	Exon 6 of 6	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.843G>C	p.Leu281Phe	missense	Exon 7 of 7	ENSP00000242576.3	P13051-1
	UNG	ENST00000336865.6	TSL:1	c.816G>C	p.Leu272Phe	missense	Exon 6 of 6	ENSP00000337398.2	P13051-2
	UNG	ENST00000446767.2	TSL:1	n.*292G>C		non_coding_transcript_exon	Exon 5 of 5	ENSP00000400287.2	Q68DM5

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	Uncertain	0.50
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	19
DANN	Benign	0.80
DEOGEN2	Uncertain	0.49	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.051	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.14
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.17
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.025	D
Varity_R		0.42
gMVP		0.70
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr12-109547675;