rs7444

Positions:

• chr22-21622645-T-C

Variant summary

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

The NM_003347.4(UBE2L3):​c.*976T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 153,146 control chromosomes in the GnomAD database, including 9,374 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 0.32 (9320 hom., cov: 32)
  • Exomes 𝑓: 0.29 (54 hom.)
• Consequence: UBE2L3 NM_003347.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.317

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]

UBE2L3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE2L3	NM_003347.4	c.*976T>C		3_prime_UTR_variant	4/4	ENST00000342192.9	NP_003338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE2L3	ENST00000342192.9	c.*976T>C		3_prime_UTR_variant	4/4	1	NM_003347.4	ENSP00000344259.5
UBE2L3	ENST00000458578.6	c.*976T>C		3_prime_UTR_variant	4/4	2		ENSP00000400906.2
UBE2L3	ENST00000545681.2	c.*976T>C		3_prime_UTR_variant	3/3	2		ENSP00000445931.1
UBE2L3	ENST00000496722.1	n.2062T>C		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48987 AN: 151960 Hom.: 9277 Cov.: 32

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.296

GnomAD4 exome AF: 0.289 AC: 309 AN: 1068 Hom.: 54 Cov.: 0 AF XY: 0.301 AC XY: 181 AN XY: 602

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.300

Gnomad4 EAS exome AF: 0.289

Gnomad4 SAS exome AF: 0.750

Gnomad4 FIN exome AF: 0.346

Gnomad4 NFE exome AF: 0.239

Gnomad4 OTH exome AF: 0.289

GnomAD4 genome AF: 0.323 AC: 49083 AN: 152078 Hom.: 9320 Cov.: 32 AF XY: 0.333 AC XY: 24786 AN XY: 74340

Gnomad4 AFR AF: 0.490

Gnomad4 AMR AF: 0.363

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.506

Gnomad4 SAS AF: 0.394

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.197

Gnomad4 OTH AF: 0.302

Alfa AF: 0.242 Hom.: 4674

Bravo AF: 0.333

Asia WGS AF: 0.502 AC: 1745 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.3
DANN	Benign	0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs7444; hg19: chr22-21976934;