3-23294959-C-A

Position:

• chr3-23294959-C-A

Variant summary

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

The NM_152653.4(UBE2E2):​c.227+77647C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 151,928 control chromosomes in the GnomAD database, including 1,813 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 0.15 (1813 hom., cov: 32)
• Consequence: UBE2E2 NM_152653.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0500

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE2E2	NM_152653.4	c.227+77647C>A		intron_variant		ENST00000396703.6	NP_689866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE2E2	ENST00000396703.6	c.227+77647C>A		intron_variant		1	NM_152653.4	ENSP00000379931	P1
UBE2E2	ENST00000335798.8	c.227+77647C>A		intron_variant, NMD_transcript_variant		1		ENSP00000338340
UBE2E2	ENST00000425792.5	c.227+77647C>A		intron_variant		2		ENSP00000401053	P1
UBE2E2	ENST00000452894.5	c.228-28556C>A		intron_variant		3		ENSP00000392800

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22518 AN: 151812 Hom.: 1811 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.0758

Gnomad AMR AF: 0.0954

Gnomad ASJ AF: 0.0942

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.148 AC: 22536 AN: 151928 Hom.: 1813 Cov.: 32 AF XY: 0.152 AC XY: 11293 AN XY: 74232

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.0954

Gnomad4 ASJ AF: 0.0942

Gnomad4 EAS AF: 0.190

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.190

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.136

Alfa AF: 0.115 Hom.: 2228

Bravo AF: 0.143

Asia WGS AF: 0.226 AC: 787 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.8
DANN	Benign	0.45

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: rs7612463; hg19: chr3-23336450;