22-21610935-A-G

Variant names:

• chr22-21610935-A-G
• NM_003347.4:c.202A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003347.4(UBE2L3):​c.202A>G​(p.Ile68Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UBE2L3 NM_003347.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.21

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23615092).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE2L3	NM_003347.4	c.202A>G	p.Ile68Val	missense_variant	Exon 3 of 4	ENST00000342192.9	NP_003338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE2L3	ENST00000342192.9	c.202A>G	p.Ile68Val	missense_variant	Exon 3 of 4	1	NM_003347.4	ENSP00000344259.5

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

Dec 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.202A>G (p.I68V) alteration is located in exon 3 (coding exon 3) of the UBE2L3 gene. This alteration results from a A to G substitution at nucleotide position 202, causing the isoleucine (I) at amino acid position 68 to be replaced by a valine (V). 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	0.18
BayesDel_addAF	Uncertain	0.081	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	.;T;.
Eigen	Benign	-0.18
Eigen_PC	Benign	0.085
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.81	T;T;T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0050	.;N;.
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.50	N;N;N
REVEL	Benign	0.20
Sift	Benign	0.47	T;T;T
Sift4G	Benign	0.89	T;T;T
Polyphen		0.0	.;B;.
Vest4		0.41
MutPred		0.54		.;Loss of sheet (P = 0.0817);.;
MVP		0.87
MPC		1.7
ClinPred		0.71	D
GERP RS		5.4
Varity_R		0.13
gMVP		0.62

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: chr22-21965224;