Variant 7-157201795-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_014671.3(UBE3C):c.1406G>A(p.Arg469Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00106 in 1,610,790 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00080 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0011 ( 2 hom. )

Consequence

UBE3C
NM_014671.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.10

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.019501).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
UBE3C	NM_014671.3 linkuse as main transcript	c.1406G>A	p.Arg469Gln	missense_variant	11/23	ENST00000348165.10	NP_055486.2
UBE3C	XM_047421072.1 linkuse as main transcript	c.1343G>A	p.Arg448Gln	missense_variant	11/23		XP_047277028.1
UBE3C	XM_005249564.5 linkuse as main transcript	c.1331G>A	p.Arg444Gln	missense_variant	10/22		XP_005249621.1
UBE3C	XM_047421073.1 linkuse as main transcript	c.1406G>A	p.Arg469Gln	missense_variant	11/16		XP_047277029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE3C	ENST00000348165.10 linkuse as main transcript	c.1406G>A	p.Arg469Gln	missense_variant	11/23	1	NM_014671.3	ENSP00000309198	P1	Q15386-1

Frequencies

GnomAD3 genomes

AF:

0.000803

AC:

122

AN:

151850

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000416

Gnomad FIN

AF:

0.0000948

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00153

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000722

AC:

180

AN:

249260

Hom.:

AF XY:

0.000727

AC XY:

AN XY:

134868

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000147

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000198

Gnomad FIN exome

AF:

0.0000944

Gnomad NFE exome

AF:

0.00131

Gnomad OTH exome

AF:

0.000658

GnomAD4 exome

AF:

0.00109

AC:

1589

AN:

1458822

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

777

AN XY:

725832

show subpopulations

Gnomad4 AFR exome

AF:

0.000300

Gnomad4 AMR exome

AF:

0.000158

Gnomad4 ASJ exome

AF:

0.00153

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000198

Gnomad4 FIN exome

AF:

0.0000762

Gnomad4 NFE exome

AF:

0.00131

Gnomad4 OTH exome

AF:

0.000929

GnomAD4 genome

AF:

0.000803

AC:

122

AN:

151968

Hom.:

Cov.:

AF XY:

0.000565

AC XY:

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.000266

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.0000948

Gnomad4 NFE

AF:

0.00153

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00125

Hom.:

Bravo

AF:

0.000808

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00163

AC:

ExAC

AF:

0.000675

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00164

EpiControl

AF:

0.00149

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2021

The c.1406G>A (p.R469Q) alteration is located in exon 11 (coding exon 11) of the UBE3C gene. This alteration results from a G to A substitution at nucleotide position 1406, causing the arginine (R) at amino acid position 469 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.12

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.24

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.0080

MetaRNN

Benign

0.020

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

MutationTaster

Benign

0.83

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.23

REVEL

Benign

0.053

Sift

Benign

0.77

Sift4G

Benign

0.68

Polyphen

0.0010

Vest4

0.21

MVP

0.068

MPC

0.23

ClinPred

0.015

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.020

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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