3-23531115-A-T

Variant names:

• chr3-23531115-A-T
• rs2173460
• NM_152653.4:c.361-1439A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152653.4(UBE2E2):​c.361-1439A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,946 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: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: UBE2E2 NM_152653.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.144
• Publications: 3 publications found

Genes affected

UBE2E2 (HGNC:12478): (ubiquitin conjugating enzyme E2 E2) Enables ISG15 transferase activity and ubiquitin conjugating enzyme activity. Involved in protein modification by small protein conjugation. Acts upstream of or within cellular response to DNA damage stimulus and positive regulation of G1/S transition of mitotic cell cycle. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE2E2	NM_152653.4	c.361-1439A>T		intron_variant	Intron 4 of 5	ENST00000396703.6	NP_689866.1
UBE2E2	NM_001370225.1	c.361-1439A>T		intron_variant	Intron 4 of 5		NP_001357154.1
UBE2E2	NM_001370226.1	c.361-1439A>T		intron_variant	Intron 4 of 5		NP_001357155.1
UBE2E2	XM_047448843.1	c.361-1439A>T		intron_variant	Intron 4 of 5		XP_047304799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE2E2	ENST00000396703.6	c.361-1439A>T		intron_variant	Intron 4 of 5	1	NM_152653.4	ENSP00000379931.1
UBE2E2	ENST00000335798.8	n.228-1439A>T		intron_variant	Intron 3 of 4	1		ENSP00000338340.4
UBE2E2	ENST00000425792.5	c.361-1439A>T		intron_variant	Intron 4 of 5	2		ENSP00000401053.1
UBE2E2	ENST00000452894.5	c.433-1439A>T		intron_variant	Intron 5 of 5	3		ENSP00000392800.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151946 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000948

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151946 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74200

African (AFR) AF: 0.00 AC: 0 AN: 41356

American (AMR) AF: 0.00 AC: 0 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.0000948 AC: 1 AN: 10544

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 1083

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.0
DANN	Benign	0.63
PhyloP100		0.14

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

Other links and lift over

dbSNP: rs2173460; hg19: chr3-23572606;