rs1078423

Variant names:

• chr12-109532259-A-C
• rs1078423
• NM_130466.4:c.2923-1207A>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.2923-1207A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0803 in 152,276 control chromosomes in the GnomAD database, including 1,110 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 0.080 (1110 hom., cov: 32)
• Consequence: UBE3B NM_130466.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.204
• Publications: 1 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), Orphanet, ClinGen, G2P, Illumina

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.217 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE3B	NM_130466.4	MANE Select	c.2923-1207A>C		intron	N/A	NP_569733.2
	UBE3B	NM_183415.3		c.2923-1207A>C		intron	N/A	NP_904324.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE3B	ENST00000342494.8	TSL:1 MANE Select	c.2923-1207A>C		intron	N/A	ENSP00000340596.3
	UBE3B	ENST00000434735.6	TSL:1	c.2923-1207A>C		intron	N/A	ENSP00000391529.2
	UBE3B	ENST00000449510.6	TSL:5	n.*904-1207A>C		intron	N/A	ENSP00000395802.2

Frequencies

GnomAD3 genomes AF: 0.0801 AC: 12193 AN: 152158 Hom.: 1097 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0989

Gnomad ASJ AF: 0.00663

Gnomad EAS AF: 0.0666

Gnomad SAS AF: 0.0147

Gnomad FIN AF: 0.0118

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0124

Gnomad OTH AF: 0.0669

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

GnomAD4 genome AF: 0.0803 AC: 12234 AN: 152276 Hom.: 1110 Cov.: 32 AF XY: 0.0788 AC XY: 5868 AN XY: 74452

African (AFR) AF: 0.220 AC: 9157 AN: 41538

American (AMR) AF: 0.0996 AC: 1524 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00663 AC: 23 AN: 3470

East Asian (EAS) AF: 0.0662 AC: 343 AN: 5180

South Asian (SAS) AF: 0.0145 AC: 70 AN: 4824

European-Finnish (FIN) AF: 0.0118 AC: 125 AN: 10620

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0124 AC: 845 AN: 68026

Other (OTH) AF: 0.0662 AC: 140 AN: 2116

Alfa AF: 0.0572 Hom.: 93

Bravo AF: 0.0943

Asia WGS AF: 0.0450 AC: 158 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.47
PhyloP100		-0.20
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

Other links and lift over

dbSNP: rs1078423; hg19: chr12-109970064;