rs780715298
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_130839.5(UBE3A):c.570G>T(p.Lys190Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_130839.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UBE3A | NM_130839.5 | c.570G>T | p.Lys190Asn | missense_variant | 6/13 | ENST00000648336.2 | |
SNHG14 | NR_146177.1 | n.18393-19992C>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UBE3A | ENST00000648336.2 | c.570G>T | p.Lys190Asn | missense_variant | 6/13 | NM_130839.5 | P1 | ||
SNHG14 | ENST00000656420.1 | n.5457-47184C>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152068Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251384Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135858
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461858Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727228
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152068Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74306
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 24, 2022 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Angelman syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 09, 2023 | This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 170 of the UBE3A protein (p.Lys170Asn). This variant is present in population databases (rs780715298, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with UBE3A-related conditions. ClinVar contains an entry for this variant (Variation ID: 528366). 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. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at