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

Variant summary

Our verdict is Benign. Variant got -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. 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

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 made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant X-143884255-C-G is Benign according to our data. Variant chrX-143884255-C-G is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE2NL	NR_121210.1 link	n.185C>G		non_coding_transcript_exon_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE2NL	ENST00000618570.1 link	c.155C>G	p.Thr52Ser	missense_variant	Exon 1 of 1	6		ENSP00000488314.1

Frequencies

GnomAD3 genomes

AF:

0.00669

AC:

755

AN:

112820

Hom.:

Cov.:

AF XY:

0.00924

AC XY:

323

AN XY:

34970

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

GnomAD3 exomes

AF:

0.00726

AC:

1333

AN:

183491

Hom.:

AF XY:

0.00539

AC XY:

366

AN XY:

67923

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 SAS exome

AF:

0.000629

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

Gnomad4 AFR exome

AF:

0.000455

Gnomad4 AMR exome

AF:

0.0398

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0256

Gnomad4 SAS exome

AF:

0.000960

Gnomad4 FIN exome

AF:

0.0000247

Gnomad4 NFE exome

AF:

0.0000689

Gnomad4 OTH exome

AF:

0.00223

GnomAD4 genome

AF:

0.00671

AC:

757

AN:

112874

Hom.:

Cov.:

AF XY:

0.00928

AC XY:

325

AN XY:

35034

show subpopulations

Gnomad4 AFR

AF:

0.000770

Gnomad4 AMR

AF:

0.0619

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0124

Gnomad4 SAS

AF:

0.00215

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000131

Gnomad4 OTH

AF:

0.00850

Alfa

AF:

0.00156

Hom.:

Bravo

AF:

0.00952

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 16, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.83

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over