rs147145506
Variant summary
Our verdict is Uncertain significance. Variant got -1 ACMG points: 0P and 1B. BP4
This summary comes from the ClinGen Evidence Repository: The c.532G>T p.Ala178Ser variant in UBE3A (NM_130838.2) is present in gnomAD v2.1.1 at a frequency of 0.0023% in the European (non-Finnish) sub population (no criteria met). Computational analysis prediction tools suggest that the p.Ala178Ser variant does not have a deleterious impact; however this information does not predict clinical significance on its own. In summary, the c.926A>G p.Asn309Ser variant in UBE3A is classified as a Variant of Uncertain Significance based on the ACMG/AMP criteria (BP4). LINK:https://erepo.genome.network/evrepo/ui/classification/CA267785992/MONDO:0007113/032
Frequency
Consequence
NM_130839.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UBE3A | NM_130839.5 | c.592G>T | p.Ala198Ser | missense_variant | 6/13 | ENST00000648336.2 | |
SNHG14 | NR_146177.1 | n.18393-20014C>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UBE3A | ENST00000648336.2 | c.592G>T | p.Ala198Ser | missense_variant | 6/13 | NM_130839.5 | P1 | ||
SNHG14 | ENST00000656420.1 | n.5457-47206C>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152182Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251406Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135862
GnomAD4 exome AF: 0.0000595 AC: 87AN: 1461864Hom.: 0 Cov.: 33 AF XY: 0.0000688 AC XY: 50AN XY: 727230
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74350
ClinVar
Submissions by phenotype
Angelman syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 17, 2023 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on UBE3A protein function. ClinVar contains an entry for this variant (Variation ID: 850340). This variant has not been reported in the literature in individuals affected with UBE3A-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.002%). This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 178 of the UBE3A protein (p.Ala178Ser). - |
Uncertain significance, reviewed by expert panel | curation | ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel | Jun 15, 2023 | The c.532G>T p.Ala178Ser variant in UBE3A (NM_130838.2) is present in gnomAD v2.1.1 at a frequency of 0.0023% in the European (non-Finnish) sub population (no criteria met). Computational analysis prediction tools suggest that the p.Ala178Ser variant does not have a deleterious impact; however this information does not predict clinical significance on its own. In summary, the c.926A>G p.Asn309Ser variant in UBE3A is classified as a Variant of Uncertain Significance based on the ACMG/AMP criteria (BP4). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 26, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at