rs886039757
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_024818.6(UBA5):c.904C>T(p.Gln302Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000684 in 1,461,430 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 Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
UBA5
NM_024818.6 stop_gained
NM_024818.6 stop_gained
Scores
5
1
1
Clinical Significance
Conservation
PhyloP100: 5.78
Genes affected
UBA5 (HGNC:23230): (ubiquitin like modifier activating enzyme 5) This gene encodes a member of the E1-like ubiquitin-activating enzyme family. This protein activates ubiquitin-fold modifier 1, a ubiquitin-like post-translational modifier protein, via the formation of a high-energy thioester bond. Alternative splicing results in multiple transcript variants. A pseudogene of this gene has been identified on chromosome 1. [provided by RefSeq, Feb 2016]
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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 3-132675339-C-T is Pathogenic according to our data. Variant chr3-132675339-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 265750.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-132675339-C-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UBA5 | NM_024818.6 | c.904C>T | p.Gln302Ter | stop_gained | 9/12 | ENST00000356232.10 | |
NPHP3-ACAD11 | NR_037804.1 | n.3995+6575G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UBA5 | ENST00000356232.10 | c.904C>T | p.Gln302Ter | stop_gained | 9/12 | 1 | NM_024818.6 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461430Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727018
GnomAD4 exome
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1
AN:
1461430
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Cov.:
31
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1
AN XY:
727018
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
UBA5-related disorder Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 24, 2023 | The UBA5 c.904C>T variant is predicted to result in premature protein termination (p.Gln302*). This variant has been reported in the compound heterozygous state in two siblings with early-onset encephalopathy (Family A, Colin et al. 2016. PubMed ID: 27545681). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Nonsense variants in UBA5 are expected to be pathogenic. This variant is interpreted as likely pathogenic. - |
Developmental and epileptic encephalopathy, 44 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 19, 2020 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
A;A;A;A;A
Vest4
GERP RS
Splicing
Name
Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: 44
Find out detailed SpliceAI scores and Pangolin per-transcript scores at