chr22-21566528-G-C

Position:

• chr22-21566528-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001256355.1(UBE2L3):​c.201+16878G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 151,466 control chromosomes in the GnomAD database, including 3,419 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.18 (3419 hom., cov: 29)
• Consequence: UBE2L3 NM_001256355.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.248

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 22-21566528-G-C is Benign according to our data. Variant chr22-21566528-G-C is described in ClinVar as [Benign]. Clinvar id is 1291200.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE2L3	NM_001256355.1	c.201+16878G>C		intron_variant			NP_001243284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE2L3	ENST00000458578.6	c.201+16878G>C		intron_variant		2		ENSP00000400906

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27899 AN: 151348 Hom.: 3413 Cov.: 29

Gnomad AFR AF: 0.0528

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.184 AC: 27898 AN: 151466 Hom.: 3419 Cov.: 29 AF XY: 0.195 AC XY: 14421 AN XY: 73946

Gnomad4 AFR AF: 0.0527

Gnomad4 AMR AF: 0.304

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.319

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.194

Alfa AF: 0.0908 Hom.: 127

Bravo AF: 0.183

Asia WGS AF: 0.327 AC: 1135 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 26, 2021

This variant is associated with the following publications: (PMID: 30614547) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.6
DANN	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs59391722; hg19: chr22-21920817; COSMIC: COSV60537969; COSMIC: COSV60537969;