rs2058807

Variant names:

• chr12-109535468-T-C
• rs2058807
• NM_130466.4:c.*686T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 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: G2P, Labcorp Genetics (formerly Invitae), Illumina, ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE3B	NM_130466.4	MANE Select	c.*686T>C		3_prime_UTR	Exon 28 of 28	NP_569733.2
	UBE3B	NM_183415.3		c.*686T>C		3_prime_UTR	Exon 28 of 28	NP_904324.1	Q7Z3V4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE3B	ENST00000342494.8	TSL:1 MANE Select	c.*686T>C		3_prime_UTR	Exon 28 of 28	ENSP00000340596.3	Q7Z3V4-1
	UBE3B	ENST00000434735.6	TSL:1	c.*686T>C		3_prime_UTR	Exon 28 of 28	ENSP00000391529.2	Q7Z3V4-1
	UBE3B	ENST00000861742.1		c.*686T>C		3_prime_UTR	Exon 29 of 29	ENSP00000531801.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 1.00 AC: 2 AN: 2

European-Finnish (FIN) AF: 0.500 AC: 2 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 26 AN: 52

Other (OTH) AF: 0.500 AC: 2 AN: 4

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

African (AFR) AF: 0.736 AC: 30552 AN: 41526

American (AMR) AF: 0.504 AC: 7693 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1848 AN: 3468

East Asian (EAS) AF: 0.298 AC: 1534 AN: 5146

South Asian (SAS) AF: 0.389 AC: 1873 AN: 4820

European-Finnish (FIN) AF: 0.465 AC: 4914 AN: 10578

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.537 AC: 36457 AN: 67936

Other (OTH) AF: 0.584 AC: 1228 AN: 2104

Alfa AF: 0.568 Hom.: 33947

Bravo AF: 0.584

Asia WGS AF: 0.387 AC: 1344 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.9
DANN	Benign	0.45
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2058807;

hg19: chr12-109973273;