11-57554507-G-T

Position:

• chr11-57554507-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004223.5(UBE2L6):​c.240C>A​(p.Asp80Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UBE2L6 NM_004223.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.893

Genes affected

UBE2L6 (HGNC:12490): (ubiquitin conjugating enzyme E2 L6) 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: ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s) and ubiquitin-protein ligases (E3s). This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. This enzyme is highly similar in primary structure to the enzyme encoded by the UBE2L3 gene. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, May 2011]

UBE2L6 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.296772).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE2L6	NM_004223.5	c.240C>A	p.Asp80Glu	missense_variant	3/4	ENST00000287156.9	NP_004214.1
UBE2L6	NM_198183.3	c.42C>A	p.Asp14Glu	missense_variant	3/4		NP_937826.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE2L6	ENST00000287156.9	c.240C>A	p.Asp80Glu	missense_variant	3/4	1	NM_004223.5	ENSP00000287156.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 16, 2021

The c.240C>A (p.D80E) alteration is located in exon 3 (coding exon 3) of the UBE2L6 gene. This alteration results from a C to A substitution at nucleotide position 240, causing the aspartic acid (D) at amino acid position 80 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	1.9
DANN	Benign	0.97
DEOGEN2	Benign	0.14	.;T;T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.13	N
LIST_S2	Uncertain	0.96	D;D;D;D
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.30	T;T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.8	.;M;.;.
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-3.5	D;D;D;D
REVEL	Benign	0.062
Sift	Uncertain	0.0030	D;D;D;D
Sift4G	Uncertain	0.0060	D;D;.;.
Polyphen		0.016	.;B;.;.
Vest4		0.23
MutPred		0.65		.;Loss of catalytic residue at D80 (P = 0.029);.;.;
MVP		0.42
MPC		0.30
ClinPred		0.49	T
GERP RS		-6.2
Varity_R		0.31
gMVP		0.52

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-57321980;