NM_130839.5:c.1007T>C
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PS2PP4
This summary comes from the ClinGen Evidence Repository: The c.947T>C p.(Met316Thr) variant in UBE3A (NM_130838.2) is present in gnomAD v2.1.1 at a frequency of 0.003% in the Latino/Admixed sub population (no criteria met). The p.(Met316Thr) variant in UBE3A has been reported as a de novo occurrence (biological parentage confirmed) in an individual with Angelman syndrome (PMID 27864847) (PS2, PP4), however the gnomAD frequency of this variant means that the PS4 criterion cannot be applied. Computational prediction analysis tools are inconclusive for this variant. In summary, the c.947T>C p.(Met316Thr) variant in UBE3A is classified as a variant of uncertain significance based on the ACMG/AMP criteria (PS2, PP4). LINK:https://erepo.genome.network/evrepo/ui/classification/CA279176/MONDO:0007113/016
Frequency
Consequence
NM_130839.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251340Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135842
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461846Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 727224
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Angelman syndrome Pathogenic:1Uncertain:2
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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). ClinVar contains an entry for this variant (Variation ID: 217366). 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 0.003%). This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 316 of the UBE3A protein (p.Met316Thr). -
Correct nomenclature and coordinates: Chr15(GRCh37):g.25616383A>G NM_130839.5(UBE3A):c.1007T>C p.(Leu293Pro) The variant is reported in Parrini et al 2017, PMID 27864847 (Pt 628N, Table S12) -
The c.947T>C p.(Met316Thr) variant in UBE3A (NM_130838.2) is present in gnomAD v2.1.1 at a frequency of 0.003% in the Latino/Admixed sub population (no criteria met). The p.(Met316Thr) variant in UBE3A has been reported as a de novo occurrence (biological parentage confirmed) in an individual with Angelman syndrome (PMID 27864847) (PS2, PP4), however the gnomAD frequency of this variant means that the PS4 criterion cannot be applied. Computational prediction analysis tools are inconclusive for this variant. In summary, the c.947T>C p.(Met316Thr) variant in UBE3A is classified as a variant of uncertain significance based on the ACMG/AMP criteria (PS2, PP4). -
not specified Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at