rs775981553

Variant names:

• chr12-109483612-G-A
• rs775981553
• NM_130466.4:c.61G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-109483612-G-A
• chr12-109483612-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_130466.4(UBE3B):​c.61G>A​(p.Glu21Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: UBE3B NM_130466.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.82

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE3B	NM_130466.4	c.61G>A	p.Glu21Lys	missense_variant	Exon 3 of 28	ENST00000342494.8	NP_569733.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE3B	ENST00000342494.8	c.61G>A	p.Glu21Lys	missense_variant	Exon 3 of 28	1	NM_130466.4	ENSP00000340596.3
UBE3B	ENST00000449510.6	n.61G>A		non_coding_transcript_exon_variant	Exon 3 of 29	5		ENSP00000395802.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.084	T;.;T;T;.;.;T
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.97	.;.;D;D;.;D;D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.53	D;D;D;D;D;D;D
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.6	M;M;.;M;M;M;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.4	N;N;N;N;N;N;N
REVEL	Uncertain	0.30
Sift	Uncertain	0.021	D;D;D;D;D;D;D
Sift4G	Uncertain	0.060	T;D;D;T;D;D;D
Polyphen		0.97	D;D;.;D;D;D;D
Vest4		0.89
MutPred		0.37		Gain of MoRF binding (P = 0.0153);Gain of MoRF binding (P = 0.0153);Gain of MoRF binding (P = 0.0153);Gain of MoRF binding (P = 0.0153);Gain of MoRF binding (P = 0.0153);Gain of MoRF binding (P = 0.0153);Gain of MoRF binding (P = 0.0153);
MVP		0.69
MPC		0.62
ClinPred		0.94	D
GERP RS		5.4
Varity_R		0.34
gMVP		0.71

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: rs775981553; hg19: chr12-109921417;