15-25338938-T-C
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2
The NM_130839.5(UBE3A):c.*199A>G variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.00144 in 378,708 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0017 ( 3 hom., cov: 32)
Exomes 𝑓: 0.0013 ( 3 hom. )
Consequence
UBE3A
NM_130839.5 3_prime_UTR
NM_130839.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 6.15
Genes affected
UBE3A (HGNC:12496): (ubiquitin protein ligase E3A) This gene encodes an E3 ubiquitin-protein ligase, part of the ubiquitin protein degradation system. This imprinted gene is maternally expressed in brain and biallelically expressed in other tissues. Maternally inherited deletion of this gene causes Angelman Syndrome, characterized by severe motor and intellectual retardation, ataxia, hypotonia, epilepsy, absence of speech, and characteristic facies. The protein also interacts with the E6 protein of human papillomavirus types 16 and 18, resulting in ubiquitination and proteolysis of tumor protein p53. Alternative splicing of this gene results in three transcript variants encoding three isoforms with different N-termini. Additional transcript variants have been described, but their full length nature has not been determined. [provided by RefSeq, Jul 2008]
SNHG14 (HGNC:37462): (small nucleolar RNA host gene 14) This gene is located within the Prader-Willi critical region and produces a long, spliced paternally-imprinted RNA that initiates within a common upstream promoter region shared by the SNRPN (small nuclear ribonucleoprotein polypeptide N) and SNURF genes. This transcript serves as a host RNA for the small nucleolar RNA, C/D box 115 and 116 clusters. This RNA extends in antisense into the region of the ubiquitin protein ligase E3A gene (UBE3A), and is thought to regulate imprinted expression of UBE3A in the brain. This transcript undergoes extensive alternative splicing, and may initiate and terminate at multiple locations within this genomic region. The full-length structure of all splice forms is not determined. [provided by RefSeq, Mar 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.23).
BP6
Variant 15-25338938-T-C is Benign according to our data. Variant chr15-25338938-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1189552.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 260 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UBE3A | NM_130839.5 | c.*199A>G | 3_prime_UTR_variant | 13/13 | ENST00000648336.2 | ||
SNHG14 | NR_146177.1 | n.18393-52658T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UBE3A | ENST00000648336.2 | c.*199A>G | 3_prime_UTR_variant | 13/13 | NM_130839.5 | P1 | |||
SNHG14 | ENST00000656420.1 | n.5456+60054T>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.00171 AC: 260AN: 152110Hom.: 3 Cov.: 32
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GnomAD4 exome AF: 0.00126 AC: 286AN: 226480Hom.: 3 Cov.: 4 AF XY: 0.00101 AC XY: 118AN XY: 117386
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GnomAD4 genome AF: 0.00171 AC: 260AN: 152228Hom.: 3 Cov.: 32 AF XY: 0.00253 AC XY: 188AN XY: 74440
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 15, 2019 | - - |
Computational scores
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Benign
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DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at