Variant chr7-157174949-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014671.3(UBE3C):c.373A>G(p.Ser125Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000112 in 1,612,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000090 ( 0 hom. )

Consequence

UBE3C
NM_014671.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.10

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.030456632).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
UBE3C	NM_014671.3 linkuse as main transcript	c.373A>G	p.Ser125Gly	missense_variant	5/23	ENST00000348165.10	NP_055486.2
UBE3C	XM_047421072.1 linkuse as main transcript	c.310A>G	p.Ser104Gly	missense_variant	5/23		XP_047277028.1
UBE3C	XM_005249564.5 linkuse as main transcript	c.298A>G	p.Ser100Gly	missense_variant	4/22		XP_005249621.1
UBE3C	XM_047421073.1 linkuse as main transcript	c.373A>G	p.Ser125Gly	missense_variant	5/16		XP_047277029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE3C	ENST00000348165.10 linkuse as main transcript	c.373A>G	p.Ser125Gly	missense_variant	5/23	1	NM_014671.3	ENSP00000309198	P1	Q15386-1
UBE3C	ENST00000389103.4 linkuse as main transcript	c.244A>G	p.Ser82Gly	missense_variant	3/9	5		ENSP00000373755		Q15386-3

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000124

AC:

AN:

250178

Hom.:

AF XY:

0.000111

AC XY:

AN XY:

135236

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.0000293

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000132

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000617

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000904

AC:

132

AN:

1460522

Hom.:

Cov.:

AF XY:

0.0000895

AC XY:

AN XY:

726516

show subpopulations

Gnomad4 AFR exome

AF:

0.00138

Gnomad4 AMR exome

AF:

0.0000225

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000466

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000558

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000322

AC:

AN:

152122

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.00101

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000161

Hom.:

Bravo

AF:

0.000495

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000115

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

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

Feb 17, 2023

The c.373A>G (p.S125G) alteration is located in exon 5 (coding exon 5) of the UBE3C gene. This alteration results from a A to G substitution at nucleotide position 373, causing the serine (S) at amino acid position 125 to be replaced by a glycine (G). 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

0.074

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.19

T;.;.

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.090

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.91

D;D;.

M_CAP

Benign

0.0057

MetaRNN

Benign

0.030

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;.;.

MutationTaster

Benign

0.88

D;D

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.7

N;.;N

REVEL

Benign

0.042

Sift

Benign

0.14

T;.;T

Sift4G

Benign

0.35

T;T;T

Polyphen

0.025

B;B;B

Vest4

0.25

MVP

0.15

MPC

0.19

ClinPred

0.023

GERP RS

4.8

Varity_R

0.14

gMVP

0.13

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