chr15-25339114-G-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_130839.5(UBE3A):​c.*23C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0085 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

UBE3A
NM_130839.5 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.00
Variant links:
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 Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
Variant 15-25339114-G-T is Benign according to our data. Variant chr15-25339114-G-T is described in ClinVar as [Benign]. Clinvar id is 1292518.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
UBE3ANM_130839.5 linkuse as main transcriptc.*23C>A 3_prime_UTR_variant 13/13 ENST00000648336.2
SNHG14NR_146177.1 linkuse as main transcriptn.18393-52482G>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
UBE3AENST00000648336.2 linkuse as main transcriptc.*23C>A 3_prime_UTR_variant 13/13 NM_130839.5 P1Q05086-3
SNHG14ENST00000656420.1 linkuse as main transcriptn.5456+60230G>T intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
23
AN:
135732
Hom.:
0
Cov.:
32
FAILED QC
Gnomad AFR
AF:
0.0000816
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000218
Gnomad ASJ
AF:
0.000320
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000232
Gnomad FIN
AF:
0.000932
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000114
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0184
AC:
2035
AN:
110544
Hom.:
0
AF XY:
0.0166
AC XY:
1026
AN XY:
61818
show subpopulations
Gnomad AFR exome
AF:
0.0195
Gnomad AMR exome
AF:
0.0260
Gnomad ASJ exome
AF:
0.0165
Gnomad EAS exome
AF:
0.0641
Gnomad SAS exome
AF:
0.0106
Gnomad FIN exome
AF:
0.00331
Gnomad NFE exome
AF:
0.0172
Gnomad OTH exome
AF:
0.0326
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00851
AC:
10379
AN:
1219996
Hom.:
0
Cov.:
30
AF XY:
0.00938
AC XY:
5568
AN XY:
593630
show subpopulations
Gnomad4 AFR exome
AF:
0.0115
Gnomad4 AMR exome
AF:
0.0298
Gnomad4 ASJ exome
AF:
0.0155
Gnomad4 EAS exome
AF:
0.0232
Gnomad4 SAS exome
AF:
0.0376
Gnomad4 FIN exome
AF:
0.00650
Gnomad4 NFE exome
AF:
0.00594
Gnomad4 OTH exome
AF:
0.0105
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.000169
AC:
23
AN:
135826
Hom.:
0
Cov.:
32
AF XY:
0.000197
AC XY:
13
AN XY:
65880
show subpopulations
Gnomad4 AFR
AF:
0.0000814
Gnomad4 AMR
AF:
0.000218
Gnomad4 ASJ
AF:
0.000320
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000233
Gnomad4 FIN
AF:
0.000932
Gnomad4 NFE
AF:
0.000114
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMar 06, 2020- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
0.41
DANN
Benign
0.35

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs955490436; hg19: chr15-25584261; API