12-109483869-T-C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_130466.4(UBE3B):c.170T>C(p.Ile57Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000199 in 1,610,260 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: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

UBE3B
NM_130466.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.19

Publications

0 publications found

Variant links:

Genes affected

UBE3B (HGNC:13478): (ubiquitin protein ligase E3B) The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: E1 ubiquitin-activating enzymes, E2 ubiquitin-conjugating enzymes, and E3 ubiquitin-protein ligases. This gene encodes a member of the E3 ubiquitin-conjugating enzyme family which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme and transfers the ubiquitin to the targeted substrates. A HECT (homology to E6-AP C-terminus) domain in the C-terminus of the longer isoform of this protein is the catalytic site of ubiquitin transfer and forms a complex with E2 conjugases. Shorter isoforms of this protein which lack the C-terminal HECT domain are therefore unlikely to bind E2 enzymes. Alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2012]

UBE3B Gene-Disease associations (from GenCC):

oculocerebrofacial syndrome, Kaufman type
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Illumina, ClinGen, G2P, Labcorp Genetics (formerly Invitae), Orphanet

UBE3B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25077945).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130466.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UBE3B	NM_130466.4	MANE Select	c.170T>C	p.Ile57Thr	missense	Exon 4 of 28	NP_569733.2
UBE3B	NM_183415.3		c.170T>C	p.Ile57Thr	missense	Exon 4 of 28	NP_904324.1	Q7Z3V4-1
UBE3B	NM_001270449.2		c.170T>C	p.Ile57Thr	missense	Exon 4 of 9	NP_001257378.1	Q7Z3V4-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UBE3B	ENST00000342494.8	TSL:1 MANE Select	c.170T>C	p.Ile57Thr	missense	Exon 4 of 28	ENSP00000340596.3	Q7Z3V4-1
UBE3B	ENST00000434735.6	TSL:1	c.170T>C	p.Ile57Thr	missense	Exon 4 of 28	ENSP00000391529.2	Q7Z3V4-1
UBE3B	ENST00000539599.5	TSL:1	c.170T>C	p.Ile57Thr	missense	Exon 3 of 23	ENSP00000443131.1	F5H5T5

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000161

AC:

AN:

248158

AF XY:

0.00000747

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000355

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000199

AC:

AN:

1458072

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

724732

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33376

American (AMR)

AF:

0.00

AC:

AN:

44112

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26062

East Asian (EAS)

AF:

0.00

AC:

AN:

39648

South Asian (SAS)

AF:

0.00

AC:

AN:

84976

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000252

AC:

AN:

1110428

Other (OTH)

AF:

0.0000166

AC:

AN:

60308

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41448

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.041

BayesDel_noAF

Benign

-0.19

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

M_CAP

Uncertain

0.090

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.48

MutationAssessor

Benign

0.69

PhyloP100

5.2

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.8

REVEL

Benign

0.11

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.049

Polyphen

0.41

Vest4

0.51

MutPred

0.54

Gain of phosphorylation at I57 (P = 0.0033)

MVP

0.73

MPC

0.35

ClinPred

0.29

GERP RS

5.3

Varity_R

0.14

gMVP

0.39

Mutation Taster

=70/30

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over