Variant 7-157181590-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014671.3(UBE3C):c.689G>A(p.Arg230Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

UBE3C
NM_014671.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.50

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29814756).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
UBE3C	NM_014671.3 linkuse as main transcript	c.689G>A	p.Arg230Gln	missense_variant	7/23	ENST00000348165.10	NP_055486.2
UBE3C	XM_047421072.1 linkuse as main transcript	c.626G>A	p.Arg209Gln	missense_variant	7/23		XP_047277028.1
UBE3C	XM_005249564.5 linkuse as main transcript	c.614G>A	p.Arg205Gln	missense_variant	6/22		XP_005249621.1
UBE3C	XM_047421073.1 linkuse as main transcript	c.689G>A	p.Arg230Gln	missense_variant	7/16		XP_047277029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE3C	ENST00000348165.10 linkuse as main transcript	c.689G>A	p.Arg230Gln	missense_variant	7/23	1	NM_014671.3	ENSP00000309198	P1	Q15386-1
UBE3C	ENST00000389103.4 linkuse as main transcript	c.560G>A	p.Arg187Gln	missense_variant	5/9	5		ENSP00000373755		Q15386-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461362

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726966

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Jul 25, 2023

The c.689G>A (p.R230Q) alteration is located in exon 7 (coding exon 7) of the UBE3C gene. This alteration results from a G to A substitution at nucleotide position 689, causing the arginine (R) at amino acid position 230 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

0.11

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.11

T;.;.

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.95

D;D;.

M_CAP

Benign

0.010

MetaRNN

Benign

0.30

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.40

N;.;N

REVEL

Benign

0.16

Sift

Uncertain

0.023

D;.;T

Sift4G

Uncertain

0.019

D;T;T

Polyphen

0.88

P;D;D

Vest4

0.48

MutPred

0.51

Loss of phosphorylation at S229 (P = 0.0878);.;.;

MVP

0.20

MPC

0.29

ClinPred

0.87

GERP RS

5.2

Varity_R

0.16

gMVP

0.35

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over