Genetic Variant UBE2NL:p.Thr52Ser (chrX-143884255-C-G) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The ENST00000618570.1(UBE2NL):c.155C>G(p.Thr52Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00261 in 1,211,078 control chromosomes in the GnomAD database, including 75 homozygotes. There are 1,049 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 5/7 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0067 ( 27 hom., 325 hem., cov: 24)

Exomes 𝑓: 0.0022 ( 48 hom. 724 hem. )

Consequence

UBE2NL
ENST00000618570.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.63

Publications

2 publications found

Variant links:

Genes affected

UBE2NL (HGNC:31710): (ubiquitin conjugating enzyme E2 N like (gene/pseudogene)) This gene is intronless and encodes a member of the ubiquitin-conjugating enzyme family. The protein product is 91% identical to ubiquitin-conjugating enzyme E2N, a multi-exon gene product. This locus represents a polymorphic pseudogene, where some individuals contain an allele that can encode a full-length protein, while others have a non-functional allele containing a premature stop codon (reference SNP rs237520) that truncates the coding sequence. [provided by RefSeq, Jun 2014]

UBE2NL links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.154).

BP6

Variant X-143884255-C-G is Benign according to our data. Variant chrX-143884255-C-G is described in ClinVar as Benign. ClinVar VariationId is 770314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.058 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000618570.1. 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
	UBE2NL	NR_121210.1		n.185C>G		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2NL	ENST00000618570.1	TSL:6	c.155C>G	p.Thr52Ser	missense	Exon 1 of 1	ENSP00000488314.1

Frequencies

GnomAD3 genomes

AF:

0.00669

AC:

755

AN:

112820

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0619

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0121

Gnomad SAS

AF:

0.00215

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000131

Gnomad OTH

AF:

0.00860

GnomAD2 exomes

AF:

0.00726

AC:

1333

AN:

183491

AF XY:

0.00539

show subpopulations

Gnomad AFR exome

AF:

0.000456

Gnomad AMR exome

AF:

0.0393

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0147

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000732

Gnomad OTH exome

AF:

0.00596

GnomAD4 exome

AF:

0.00219

AC:

2401

AN:

1098204

Hom.:

Cov.:

AF XY:

0.00199

AC XY:

724

AN XY:

363560

show subpopulations

African (AFR)

AF:

0.000455

AC:

AN:

26402

American (AMR)

AF:

0.0398

AC:

1402

AN:

35206

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19384

East Asian (EAS)

AF:

0.0256

AC:

773

AN:

30205

South Asian (SAS)

AF:

0.000960

AC:

AN:

54145

European-Finnish (FIN)

AF:

0.0000247

AC:

AN:

40533

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.0000689

AC:

AN:

842098

Other (OTH)

AF:

0.00223

AC:

103

AN:

46094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

123

246

370

493

616

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00671

AC:

757

AN:

112874

Hom.:

Cov.:

AF XY:

0.00928

AC XY:

325

AN XY:

35034

show subpopulations

African (AFR)

AF:

0.000770

AC:

AN:

31166

American (AMR)

AF:

0.0619

AC:

663

AN:

10713

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2660

East Asian (EAS)

AF:

0.0124

AC:

AN:

3552

South Asian (SAS)

AF:

0.00215

AC:

AN:

2785

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6215

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.000131

AC:

AN:

53350

Other (OTH)

AF:

0.00850

AC:

AN:

1530

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00156

Hom.:

Bravo

AF:

0.00952

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000237

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

5.6

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over