chr3-23887582-C-T

Variant names:

• chr3-23887582-C-T
• rs115996277
• NM_003341.5:c.219C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_003341.5(UBE2E1):​c.219C>T​(p.Gly73Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00926 in 1,611,076 control chromosomes in the GnomAD database, including 83 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0056 (5 hom., cov: 33)
  • Exomes 𝑓: 0.0096 (78 hom.)
• Consequence: UBE2E1 NM_003341.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.17
• Publications: 4 publications found

Genes affected

UBE2E1 (HGNC:12477): (ubiquitin conjugating enzyme E2 E1) 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, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. Three alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jan 2011]

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 3-23887582-C-T is Benign according to our data. Variant chr3-23887582-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 781706.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.17 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 5 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003341.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2E1	NM_003341.5	MANE Select	c.219C>T	p.Gly73Gly	synonymous	Exon 4 of 6	NP_003332.1	P51965-1
	UBE2E1	NM_182666.3		c.168C>T	p.Gly56Gly	synonymous	Exon 3 of 5	NP_872607.1	P51965-3
	UBE2E1	NM_001202476.2		c.120C>T	p.Gly40Gly	synonymous	Exon 3 of 5	NP_001189405.1	P51965-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2E1	ENST00000306627.8	TSL:1 MANE Select	c.219C>T	p.Gly73Gly	synonymous	Exon 4 of 6	ENSP00000303709.3	P51965-1
	UBE2E1	ENST00000913090.1		c.219C>T	p.Gly73Gly	synonymous	Exon 4 of 6	ENSP00000583149.1
	UBE2E1	ENST00000346855.7	TSL:3	c.168C>T	p.Gly56Gly	synonymous	Exon 3 of 5	ENSP00000329113.4	P51965-3

Frequencies

GnomAD3 genomes AF: 0.00565 AC: 860 AN: 152130 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.00212

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00445

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00340

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00955

Gnomad OTH AF: 0.00574

GnomAD2 exomes AF: 0.00556 AC: 1380 AN: 247992 AF XY: 0.00566

Gnomad AFR exome AF: 0.00179

Gnomad AMR exome AF: 0.00626

Gnomad ASJ exome AF: 0.00302

Gnomad EAS exome AF: 0.0000549

Gnomad FIN exome AF: 0.00195

Gnomad NFE exome AF: 0.00902

Gnomad OTH exome AF: 0.00742

GnomAD4 exome AF: 0.00964 AC: 14064 AN: 1458828 Hom.: 78 Cov.: 30 AF XY: 0.00935 AC XY: 6782 AN XY: 725672

African (AFR) AF: 0.00150 AC: 50 AN: 33294

American (AMR) AF: 0.00581 AC: 254 AN: 43694

Ashkenazi Jewish (ASJ) AF: 0.00238 AC: 62 AN: 26000

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39678

South Asian (SAS) AF: 0.000187 AC: 16 AN: 85496

European-Finnish (FIN) AF: 0.00197 AC: 105 AN: 53402

Middle Eastern (MID) AF: 0.000869 AC: 5 AN: 5754

European-Non Finnish (NFE) AF: 0.0117 AC: 13007 AN: 1111232

Other (OTH) AF: 0.00936 AC: 564 AN: 60278

GnomAD4 genome AF: 0.00564 AC: 859 AN: 152248 Hom.: 5 Cov.: 33 AF XY: 0.00517 AC XY: 385 AN XY: 74426

African (AFR) AF: 0.00212 AC: 88 AN: 41534

American (AMR) AF: 0.00438 AC: 67 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3468

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00340 AC: 36 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00955 AC: 650 AN: 68028

Other (OTH) AF: 0.00568 AC: 12 AN: 2112

Alfa AF: 0.00766 Hom.: 6

Bravo AF: 0.00611

EpiCase AF: 0.00987

EpiControl AF: 0.0105

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	8.4
DANN	Benign	0.85
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs115996277; hg19: chr3-23929073; COSMIC: COSV108127477; COSMIC: COSV108127477;