chr12-109483612-G-T
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1_StrongPM2PP5_Very_Strong
The NM_130466.4(UBE3B):c.61G>T(p.Glu21*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,612,716 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 (★★).
Frequency
Consequence
NM_130466.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
UBE3B | NM_130466.4 | c.61G>T | p.Glu21* | stop_gained | Exon 3 of 28 | ENST00000342494.8 | NP_569733.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152214Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000440 AC: 11AN: 249934Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135118
GnomAD4 exome AF: 0.0000110 AC: 16AN: 1460502Hom.: 0 Cov.: 31 AF XY: 0.00000551 AC XY: 4AN XY: 726588
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152214Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74356
ClinVar
Submissions by phenotype
not provided Pathogenic:3
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 25356970, 31162149, 30792901, 31847883, 24615390, 27535533) -
PVS1, PM3, PM2, PS4_Moderate -
This sequence change creates a premature translational stop signal (p.Glu21*) in the UBE3B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in UBE3B are known to be pathogenic (PMID: 23687348, 24615390). This variant is present in population databases (rs775981553, gnomAD 0.03%). This premature translational stop signal has been observed in individual(s) with Kaufman oculocerebrofacial syndrome (PMID: 24615390, 30792901). ClinVar contains an entry for this variant (Variation ID: 225041). For these reasons, this variant has been classified as Pathogenic. -
Oculocerebrofacial syndrome, Kaufman type Pathogenic:2
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The UBE3B c.61G>T (p.Glu21Ter) variant is a stop-gained variant that is predicted to result in an absent or prematurely truncated protein product, including loss of the functionally critical HECT domain. The p.Glu21Ter variant has been reported in two studies in which it was identified in a homozygous state in two unrelated individuals, one with a diagnosis of Kaufman oculocerebrofacial syndrome and one with blepharophimosis-ptosis-intellectual disability syndrome (Basal-Vanagaite et al. 2014; Farwell et al. 2015). The p.Glu21Ter variant is reported at a frequency of 0.000286 in the Latino population of the Genome Aggregation Database. Based on the collective evidence, the p.Glu21Ter variant is classified as pathogenic for Kaufman oculocerebrofacial syndrome. -
Inborn genetic diseases Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at