X-143884530-T-C

Variant names:

• chrX-143884530-T-C
• ENST00000618570.1:c.430T>C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4 BS2

The ENST00000618570.1(UBE2NL):​c.430T>C​(p.Trp144Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000082 in 1,097,279 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000082 (0 hom. 5 hem.)
• Consequence: UBE2NL ENST00000618570.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.08

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]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.13).
• BS2: High Hemizygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE2NL	NR_121210.1	n.460T>C		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	c.430T>C	p.Trp144Arg	missense_variant	Exon 1 of 1	6		ENSP00000488314.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000820 AC: 9 AN: 1097279 Hom.: 0 Cov.: 30 AF XY: 0.0000138 AC XY: 5 AN XY: 362743

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000185

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000951

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.430T>C (p.W144R) alteration is located in exon 1 (coding exon 1) of the UBE2NL gene. This alteration results from a T to C substitution at nucleotide position 430, causing the tryptophan (W) at amino acid position 144 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.13
CADD	Benign	19
DANN	Benign	0.78

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-142967632;