12-109483694-GA-AG

Variant names:

• chr12-109483694-GA-AG
• NM_130466.4:c.143_144delGAinsAG
• UBE3B p.Arg48Gln

Variant summary

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

The NM_130466.4(UBE3B):​c.143_144delGAinsAG​(p.Arg48Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: UBE3B NM_130466.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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.143_144delGAinsAG	p.Arg48Gln	missense	N/A	NP_569733.2
	UBE3B	NM_183415.3		c.143_144delGAinsAG	p.Arg48Gln	missense	N/A	NP_904324.1	Q7Z3V4-1
	UBE3B	NM_001270449.2		c.143_144delGAinsAG	p.Arg48Gln	missense	N/A	NP_001257378.1	Q7Z3V4-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE3B	ENST00000342494.8	TSL:1 MANE Select	c.143_144delGAinsAG	p.Arg48Gln	missense	N/A	ENSP00000340596.3	Q7Z3V4-1
	UBE3B	ENST00000434735.6	TSL:1	c.143_144delGAinsAG	p.Arg48Gln	missense	N/A	ENSP00000391529.2	Q7Z3V4-1
	UBE3B	ENST00000539599.5	TSL:1	c.143_144delGAinsAG	p.Arg48Gln	missense	N/A	ENSP00000443131.1	F5H5T5

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6

Splicing

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

hg19: chr12-109921499;