Variant rs8179187 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000566215.5(UBE3A):c.-153A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0769 in 1,341,490 control chromosomes in the GnomAD database, including 5,322 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.073 ( 698 hom., cov: 32)

Exomes 𝑓: 0.077 ( 4624 hom. )

Consequence

UBE3A
ENST00000566215.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.555

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]

UBE3A links:

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]

SNHG14 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE3A	NM_130839.5 linkuse as main transcript	c.21-1677A>C		intron_variant		ENST00000648336.2	NP_570854.1
SNHG14	NR_146177.1 linkuse as main transcript	n.18589-11609T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE3A	ENST00000648336.2 linkuse as main transcript	c.21-1677A>C		intron_variant			NM_130839.5	ENSP00000497572	P1	Q05086-3
SNHG14	ENST00000656420.1 linkuse as main transcript	n.5457-11609T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0732

AC:

11130

AN:

152106

Hom.:

697

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0199

Gnomad AMI

AF:

0.116

Gnomad AMR

AF:

0.131

Gnomad ASJ

AF:

0.0804

Gnomad EAS

AF:

0.311

Gnomad SAS

AF:

0.110

Gnomad FIN

AF:

0.0735

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0711

Gnomad OTH

AF:

0.0655

GnomAD3 exomes

AF:

0.109

AC:

23403

AN:

215128

Hom.:

1897

AF XY:

0.104

AC XY:

12340

AN XY:

119118

show subpopulations

Gnomad AFR exome

AF:

0.0200

Gnomad AMR exome

AF:

0.195

Gnomad ASJ exome

AF:

0.0695

Gnomad EAS exome

AF:

0.308

Gnomad SAS exome

AF:

0.103

Gnomad FIN exome

AF:

0.0797

Gnomad NFE exome

AF:

0.0692

Gnomad OTH exome

AF:

0.0921

GnomAD4 exome

AF:

0.0774

AC:

92013

AN:

1189266

Hom.:

4624

Cov.:

AF XY:

0.0777

AC XY:

45815

AN XY:

589272

show subpopulations

Gnomad4 AFR exome

AF:

0.0181

Gnomad4 AMR exome

AF:

0.192

Gnomad4 ASJ exome

AF:

0.0689

Gnomad4 EAS exome

AF:

0.310

Gnomad4 SAS exome

AF:

0.100

Gnomad4 FIN exome

AF:

0.0815

Gnomad4 NFE exome

AF:

0.0687

Gnomad4 OTH exome

AF:

0.0852

GnomAD4 genome

AF:

0.0731

AC:

11134

AN:

152224

Hom.:

698

Cov.:

AF XY:

0.0776

AC XY:

5771

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.0200

Gnomad4 AMR

AF:

0.132

Gnomad4 ASJ

AF:

0.0804

Gnomad4 EAS

AF:

0.311

Gnomad4 SAS

AF:

0.110

Gnomad4 FIN

AF:

0.0735

Gnomad4 NFE

AF:

0.0711

Gnomad4 OTH

AF:

0.0639

Alfa

AF:

0.0675

Hom.:

448

Bravo

AF:

0.0759

Asia WGS

AF:

0.187

AC:

652

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.93

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over