Variant 11-57554571-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_198183.3(UBE2L6):c.-23C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

UBE2L6
NM_198183.3 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.249

Variant links:

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 links:

UBE2L6 (HGNC:):

UBE2L6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.049604446).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE2L6	NM_004223.5 linkuse as main transcript	c.176C>T	p.Pro59Leu	missense_variant	3/4	ENST00000287156.9	NP_004214.1	O14933-1
UBE2L6	NM_198183.3 linkuse as main transcript	c.-23C>T		5_prime_UTR_premature_start_codon_gain_variant	3/4		NP_937826.1	O14933-2
UBE2L6	NM_198183.3 linkuse as main transcript	c.-23C>T		5_prime_UTR_variant	3/4		NP_937826.1	O14933-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE2L6	ENST00000287156.9 linkuse as main transcript	c.176C>T	p.Pro59Leu	missense_variant	3/4	1	NM_004223.5	ENSP00000287156.4		O14933-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251452

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2024

The c.176C>T (p.P59L) alteration is located in exon 3 (coding exon 3) of the UBE2L6 gene. This alteration results from a C to T substitution at nucleotide position 176, causing the proline (P) at amino acid position 59 to be replaced by a leucine (L). 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

Benign

0.12

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.44

CADD

Benign

0.69

DANN

Benign

0.73

DEOGEN2

Benign

0.064

T;T

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.11

LIST_S2

Uncertain

0.96

D;D

M_CAP

Benign

0.074

MetaRNN

Benign

0.050

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.91

L;.

PrimateAI

Benign

0.21

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.27

Sift

Benign

0.064

T;T

Sift4G

Benign

0.22

T;.

Polyphen

0.0010

B;.

Vest4

0.18

MutPred

0.36

Loss of catalytic residue at P58 (P = 0.0099);.;

MVP

0.16

MPC

0.34

ClinPred

0.089

GERP RS

-12

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.026

gMVP

0.33

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over