15-25339119-ATTTTG-A
Variant summary
Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2
The NM_130839.5(UBE3A):c.*13_*17delCAAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000231 in 1,429,850 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000022 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000023 ( 0 hom. )
Consequence
UBE3A
NM_130839.5 3_prime_UTR
NM_130839.5 3_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.720
Publications
0 publications found
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 was made for transcript
Our verdict: Likely_benign. The variant received -6 ACMG points.
BP6
Variant 15-25339119-ATTTTG-A is Benign according to our data. Variant chr15-25339119-ATTTTG-A is described in ClinVar as [Likely_benign]. Clinvar id is 156147.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAdExome4 at 30 AD gene.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000219 AC: 3AN: 136802Hom.: 0 Cov.: 31 show subpopulations
GnomAD3 genomes
AF:
AC:
3
AN:
136802
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
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AF:
Gnomad FIN
AF:
Gnomad MID
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Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.0000234 AC: 3AN: 128166 AF XY: 0.0000422 show subpopulations
GnomAD2 exomes
AF:
AC:
3
AN:
128166
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
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Gnomad ASJ exome
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Gnomad EAS exome
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Gnomad FIN exome
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Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000232 AC: 30AN: 1293048Hom.: 0 AF XY: 0.0000284 AC XY: 18AN XY: 632732 show subpopulations
GnomAD4 exome
AF:
AC:
30
AN:
1293048
Hom.:
AF XY:
AC XY:
18
AN XY:
632732
show subpopulations
African (AFR)
AF:
AC:
2
AN:
27556
American (AMR)
AF:
AC:
1
AN:
22732
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
21014
East Asian (EAS)
AF:
AC:
2
AN:
34128
South Asian (SAS)
AF:
AC:
1
AN:
59098
European-Finnish (FIN)
AF:
AC:
0
AN:
44386
Middle Eastern (MID)
AF:
AC:
0
AN:
4004
European-Non Finnish (NFE)
AF:
AC:
24
AN:
1027550
Other (OTH)
AF:
AC:
0
AN:
52580
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.467
Heterozygous variant carriers
0
1
3
4
6
7
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome AF: 0.0000219 AC: 3AN: 136802Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 66620 show subpopulations
GnomAD4 genome
AF:
AC:
3
AN:
136802
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
66620
show subpopulations
African (AFR)
AF:
AC:
0
AN:
36742
American (AMR)
AF:
AC:
0
AN:
13946
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3202
East Asian (EAS)
AF:
AC:
0
AN:
4744
South Asian (SAS)
AF:
AC:
0
AN:
4364
European-Finnish (FIN)
AF:
AC:
0
AN:
8896
Middle Eastern (MID)
AF:
AC:
0
AN:
290
European-Non Finnish (NFE)
AF:
AC:
2
AN:
61914
Other (OTH)
AF:
AC:
1
AN:
1900
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.508
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Likely benign
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Angelman syndrome Uncertain:1
Feb 14, 2014
Baylor Genetics
Significance:Uncertain significance
Review Status:no assertion criteria provided
Collection Method:clinical testing
possible diagnosis of Angelman syndrome -
not provided Benign:1
Jul 14, 2017
GeneDx
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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