rs772214871
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_080911.3(UNG):c.685C>T(p.Arg229Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,614,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
UNG
NM_080911.3 stop_gained
NM_080911.3 stop_gained
Scores
2
1
4
Clinical Significance
Conservation
PhyloP100: 0.275
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 12-109103495-C-T is Pathogenic according to our data. Variant chr12-109103495-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 578381.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UNG | NM_080911.3 | c.685C>T | p.Arg229Ter | stop_gained | 6/7 | ENST00000242576.7 | |
UNG | NM_003362.4 | c.658C>T | p.Arg220Ter | stop_gained | 5/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UNG | ENST00000242576.7 | c.685C>T | p.Arg229Ter | stop_gained | 6/7 | 1 | NM_080911.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152194Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251474Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135916
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461874Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727242
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hyper-IgM syndrome type 5 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Mar 06, 2019 | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in UNG are known to be pathogenic (PMID: 12958596). This variant has not been reported in the literature in individuals with UNG-related disease. This variant is present in population databases (rs772214871, ExAC 0.01%). This sequence change creates a premature translational stop signal (p.Arg229*) in the UNG gene. It is expected to result in an absent or disrupted protein product. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
MutationTaster
Benign
A;A
Vest4
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at