12-109543873-C-T

Variant names:

• chr12-109543873-C-T
• rs731178
• XM_011538961.2:c.*260C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_011538961.2(UBE3B):​c.*260C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 151,772 control chromosomes in the GnomAD database, including 25,410 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.57 (25410 hom., cov: 29)
• Consequence: UBE3B XM_011538961.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.668
• Publications: 9 publications found

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: Labcorp Genetics (formerly Invitae), ClinGen, Illumina, G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.567 AC: 85953 AN: 151658 Hom.: 25369 Cov.: 29

Gnomad AFR AF: 0.723

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.580

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.567 AC: 86055 AN: 151772 Hom.: 25410 Cov.: 29 AF XY: 0.557 AC XY: 41308 AN XY: 74168

African (AFR) AF: 0.724 AC: 29950 AN: 41388

American (AMR) AF: 0.503 AC: 7677 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 1847 AN: 3470

East Asian (EAS) AF: 0.297 AC: 1526 AN: 5142

South Asian (SAS) AF: 0.388 AC: 1859 AN: 4794

European-Finnish (FIN) AF: 0.464 AC: 4880 AN: 10512

Middle Eastern (MID) AF: 0.548 AC: 160 AN: 292

European-Non Finnish (NFE) AF: 0.536 AC: 36400 AN: 67894

Other (OTH) AF: 0.581 AC: 1224 AN: 2108

Alfa AF: 0.545 Hom.: 30073

Bravo AF: 0.581

Asia WGS AF: 0.383 AC: 1332 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.91
DANN	Benign	0.12
PhyloP100		-0.67

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs731178; hg19: chr12-109981678; COSMIC: COSV50457784;