22-21562901-G-T

Position:

• chr22-21562901-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001256355.1(UBE2L3):​c.201+13251G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 151,628 control chromosomes in the GnomAD database, including 43,429 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 0.75 (43429 hom., cov: 28)
• Consequence: UBE2L3 NM_001256355.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

Genes affected

UBE2L3 (HGNC:12488): (ubiquitin conjugating enzyme E2 L3) 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 demonstrated to participate in the ubiquitination of p53, c-Fos, and the NF-kB precursor p105 in vitro. Several alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.931 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBE2L3	NM_001256355.1	c.201+13251G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBE2L3	ENST00000458578.6	c.201+13251G>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.745 AC: 112861 AN: 151512 Hom.: 43351 Cov.: 28

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.727

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.779

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.664

Gnomad OTH AF: 0.765

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

GnomAD4 genome AF: 0.745 AC: 113000 AN: 151628 Hom.: 43429 Cov.: 28 AF XY: 0.744 AC XY: 55110 AN XY: 74056

Gnomad4 AFR AF: 0.938

Gnomad4 AMR AF: 0.727

Gnomad4 ASJ AF: 0.648

Gnomad4 EAS AF: 0.566

Gnomad4 SAS AF: 0.778

Gnomad4 FIN AF: 0.644

Gnomad4 NFE AF: 0.664

Gnomad4 OTH AF: 0.769

Alfa AF: 0.678 Hom.: 75043

Bravo AF: 0.761

Asia WGS AF: 0.742 AC: 2584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.45
DANN	Benign	0.75

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs131654; hg19: chr22-21917190;