Variant 7-157186982-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014671.3(UBE3C):c.1292C>T(p.Thr431Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,459,414 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: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

UBE3C
NM_014671.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.80

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.177957).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
UBE3C	NM_014671.3 linkuse as main transcript	c.1292C>T	p.Thr431Met	missense_variant	10/23	ENST00000348165.10	NP_055486.2
UBE3C	XM_047421072.1 linkuse as main transcript	c.1229C>T	p.Thr410Met	missense_variant	10/23		XP_047277028.1
UBE3C	XM_005249564.5 linkuse as main transcript	c.1217C>T	p.Thr406Met	missense_variant	9/22		XP_005249621.1
UBE3C	XM_047421073.1 linkuse as main transcript	c.1292C>T	p.Thr431Met	missense_variant	10/16		XP_047277029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE3C	ENST00000348165.10 linkuse as main transcript	c.1292C>T	p.Thr431Met	missense_variant	10/23	1	NM_014671.3	ENSP00000309198	P1	Q15386-1
UBE3C	ENST00000389103.4 linkuse as main transcript	c.1163C>T	p.Thr388Met	missense_variant	8/9	5		ENSP00000373755		Q15386-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000814

AC:

AN:

245640

Hom.:

AF XY:

0.00000754

AC XY:

AN XY:

132662

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000555

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000902

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1459414

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725772

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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

May 13, 2024

The c.1292C>T (p.T431M) alteration is located in exon 10 (coding exon 10) of the UBE3C gene. This alteration results from a C to T substitution at nucleotide position 1292, causing the threonine (T) at amino acid position 431 to be replaced by a methionine (M). 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

0.096

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

T;.;.

Eigen

Benign

0.055

Eigen_PC

Benign

0.13

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

D;D;.

M_CAP

Benign

0.015

MetaRNN

Benign

0.18

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.5

L;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.44

PROVEAN

Benign

-2.1

N;.;N

REVEL

Benign

0.12

Sift

Benign

0.083

T;.;D

Sift4G

Benign

0.21

T;D;D

Polyphen

0.058

B;P;P

Vest4

0.34

MutPred

0.47

Gain of MoRF binding (P = 0.0912);.;.;

MVP

0.082

MPC

0.22

ClinPred

0.56

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.084

gMVP

0.54

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