rs2058807

Positions:

• chr12-109535468-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_130466.4(UBE3B):​c.*686T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 152,116 control chromosomes in the GnomAD database, including 25,877 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 (25867 hom., cov: 33)
  • Exomes 𝑓: 0.50 (10 hom.)
• Consequence: UBE3B NM_130466.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.265

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE3B	NM_130466.4	c.*686T>C		3_prime_UTR_variant	28/28	ENST00000342494.8	NP_569733.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE3B	ENST00000342494.8	c.*686T>C		3_prime_UTR_variant	28/28	1	NM_130466.4	ENSP00000340596.3
UBE3B	ENST00000434735.6	c.*686T>C		3_prime_UTR_variant	28/28	1		ENSP00000391529.2

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86684 AN: 151932 Hom.: 25818 Cov.: 33

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.537

Gnomad OTH AF: 0.583

GnomAD4 exome AF: 0.500 AC: 33 AN: 66 Hom.: 10 Cov.: 0 AF XY: 0.500 AC XY: 22 AN XY: 44

Gnomad4 AMR exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.571 AC: 86797 AN: 152050 Hom.: 25867 Cov.: 33 AF XY: 0.561 AC XY: 41707 AN XY: 74338

Gnomad4 AFR AF: 0.736

Gnomad4 AMR AF: 0.504

Gnomad4 ASJ AF: 0.533

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.465

Gnomad4 NFE AF: 0.537

Gnomad4 OTH AF: 0.584

Alfa AF: 0.551 Hom.: 22659

Bravo AF: 0.584

Asia WGS AF: 0.387 AC: 1344 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.9
DANN	Benign	0.45

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

Other links and lift over

dbSNP: rs2058807; hg19: chr12-109973273;