15-25338938-T-C

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

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.15
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 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
UBE3ANM_130839.5 linkuse as main transcriptc.*199A>G 3_prime_UTR_variant 13/13 ENST00000648336.2
SNHG14NR_146177.1 linkuse as main transcriptn.18393-52658T>C intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
UBE3AENST00000648336.2 linkuse as main transcriptc.*199A>G 3_prime_UTR_variant 13/13 NM_130839.5 P1Q05086-3
SNHG14ENST00000656420.1 linkuse as main transcriptn.5456+60054T>C intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.00171
AC:
260
AN:
152110
Hom.:
3
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00115
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0221
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000279
Gnomad OTH
AF:
0.000478
GnomAD4 exome
AF:
0.00126
AC:
286
AN:
226480
Hom.:
3
Cov.:
4
AF XY:
0.00101
AC XY:
118
AN XY:
117386
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.000273
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0181
Gnomad4 NFE exome
AF:
0.000419
Gnomad4 OTH exome
AF:
0.000991
GnomAD4 genome
AF:
0.00171
AC:
260
AN:
152228
Hom.:
3
Cov.:
32
AF XY:
0.00253
AC XY:
188
AN XY:
74440
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00115
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0221
Gnomad4 NFE
AF:
0.000279
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000476
Hom.:
0
Bravo
AF:
0.000159
Asia WGS
AF:
0.000289
AC:
1
AN:
3476

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 submitterclinical testingGeneDxSep 15, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.23
CADD
Benign
15
DANN
Benign
0.92

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: rs182421497; hg19: chr15-25584085; API