Variant chr7-157178682-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_014671.3(UBE3C):c.459-8T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00224 in 1,611,542 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 71 hom. )

Consequence

UBE3C
NM_014671.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0003684

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.17

Variant links:

Genes affected

UBE3C (HGNC:16803): (ubiquitin protein ligase E3C) Enables ubiquitin protein ligase activity. Involved in protein polyubiquitination. Predicted to be located in nucleus. Predicted to be part of proteasome complex. [provided by Alliance of Genome Resources, Apr 2022]

UBE3C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 7-157178682-T-C is Benign according to our data. Variant chr7-157178682-T-C is described in ClinVar as [Benign]. Clinvar id is 3043379.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0014 (214/152326) while in subpopulation SAS AF= 0.0257 (124/4826). AF 95% confidence interval is 0.022. There are 4 homozygotes in gnomad4. There are 127 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
UBE3C	NM_014671.3 linkuse as main transcript	c.459-8T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000348165.10
UBE3C	XM_005249564.5 linkuse as main transcript	c.384-8T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
UBE3C	XM_047421072.1 linkuse as main transcript	c.396-8T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
UBE3C	XM_047421073.1 linkuse as main transcript	c.459-8T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBE3C	ENST00000348165.10 linkuse as main transcript	c.459-8T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_014671.3	P1	Q15386-1
UBE3C	ENST00000389103.4 linkuse as main transcript	c.330-8T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5			Q15386-3

Frequencies

GnomAD3 genomes

AF:

0.00141

AC:

214

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0257

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000955

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00392

AC:

982

AN:

250396

Hom.:

AF XY:

0.00517

AC XY:

700

AN XY:

135362

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00107

Gnomad ASJ exome

AF:

0.00161

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0257

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00117

Gnomad OTH exome

AF:

0.00213

GnomAD4 exome

AF:

0.00233

AC:

3399

AN:

1459216

Hom.:

Cov.:

AF XY:

0.00310

AC XY:

2248

AN XY:

725590

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.00114

Gnomad4 ASJ exome

AF:

0.00177

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0267

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000703

Gnomad4 OTH exome

AF:

0.00280

GnomAD4 genome

AF:

0.00140

AC:

214

AN:

152326

Hom.:

Cov.:

AF XY:

0.00171

AC XY:

127

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0257

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000955

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00108

Hom.:

Bravo

AF:

0.000793

Asia WGS

AF:

0.00837

AC:

AN:

3478

EpiCase

AF:

0.00159

EpiControl

AF:

0.00184

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

UBE3C-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 04, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00037

dbscSNV1_RF

Benign

0.054

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over