Variant 7-157181660-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_014671.3(UBE3C):c.759G>A(p.Pro253Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0637 in 1,613,138 control chromosomes in the GnomAD database, including 3,637 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.046 ( 216 hom., cov: 33)

Exomes 𝑓: 0.066 ( 3421 hom. )

Consequence

UBE3C
NM_014671.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.229

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=-0.53).

BP6

Variant 7-157181660-G-A is Benign according to our data. Variant chr7-157181660-G-A is described in ClinVar as [Benign]. Clinvar id is 3056835.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.229 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE3C	NM_014671.3 link	c.759G>A	p.Pro253Pro	synonymous_variant	7/23	ENST00000348165.10	NP_055486.2	Q15386-1
UBE3C	XM_047421072.1 link	c.696G>A	p.Pro232Pro	synonymous_variant	7/23		XP_047277028.1
UBE3C	XM_005249564.5 link	c.684G>A	p.Pro228Pro	synonymous_variant	6/22		XP_005249621.1
UBE3C	XM_047421073.1 link	c.759G>A	p.Pro253Pro	synonymous_variant	7/16		XP_047277029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE3C	ENST00000348165.10 link	c.759G>A	p.Pro253Pro	synonymous_variant	7/23	1	NM_014671.3	ENSP00000309198.8		Q15386-1
UBE3C	ENST00000389103.4 link	c.630G>A	p.Pro210Pro	synonymous_variant	5/9	5		ENSP00000373755.4		Q15386-3

Frequencies

GnomAD3 genomes

AF:

0.0459

AC:

6979

AN:

152108

Hom.:

216

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0123

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.0451

Gnomad ASJ

AF:

0.0513

Gnomad EAS

AF:

0.00519

Gnomad SAS

AF:

0.0303

Gnomad FIN

AF:

0.0453

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0710

Gnomad OTH

AF:

0.0408

GnomAD3 exomes

AF:

0.0470

AC:

11760

AN:

250060

Hom.:

342

AF XY:

0.0487

AC XY:

6586

AN XY:

135230

show subpopulations

Gnomad AFR exome

AF:

0.0112

Gnomad AMR exome

AF:

0.0278

Gnomad ASJ exome

AF:

0.0596

Gnomad EAS exome

AF:

0.00561

Gnomad SAS exome

AF:

0.0338

Gnomad FIN exome

AF:

0.0457

Gnomad NFE exome

AF:

0.0670

Gnomad OTH exome

AF:

0.0533

GnomAD4 exome

AF:

0.0656

AC:

95768

AN:

1460912

Hom.:

3421

Cov.:

AF XY:

0.0644

AC XY:

46820

AN XY:

726728

show subpopulations

Gnomad4 AFR exome

AF:

0.0108

Gnomad4 AMR exome

AF:

0.0295

Gnomad4 ASJ exome

AF:

0.0574

Gnomad4 EAS exome

AF:

0.00338

Gnomad4 SAS exome

AF:

0.0331

Gnomad4 FIN exome

AF:

0.0443

Gnomad4 NFE exome

AF:

0.0750

Gnomad4 OTH exome

AF:

0.0620

GnomAD4 genome

AF:

0.0458

AC:

6977

AN:

152226

Hom.:

216

Cov.:

AF XY:

0.0450

AC XY:

3350

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0123

Gnomad4 AMR

AF:

0.0450

Gnomad4 ASJ

AF:

0.0513

Gnomad4 EAS

AF:

0.00520

Gnomad4 SAS

AF:

0.0303

Gnomad4 FIN

AF:

0.0453

Gnomad4 NFE

AF:

0.0710

Gnomad4 OTH

AF:

0.0408

Alfa

AF:

0.0543

Hom.:

174

Bravo

AF:

0.0443

Asia WGS

AF:

0.0200

AC:

AN:

3478

EpiCase

AF:

0.0676

EpiControl

AF:

0.0694

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

UBE3C-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 13, 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

-0.53

CADD

Benign

6.0

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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