Genetic Variant UBE4A:c.2412+14_2412+23delAAAAAAAAAA (chr11-118384947-TAAAAAAAAAA-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000252108.8(UBE4A):c.2412+3_2412+12delAAAAAAAAAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000101 in 987,620 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.0000010 ( 0 hom. )

Consequence

UBE4A
ENST00000252108.8 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.09

Variant links:

Genes affected

UBE4A (HGNC:12499): (ubiquitination factor E4A) This gene encodes a member of the U-box ubiquitin ligase family. The encoded protein is involved in multiubiquitin chain assembly and plays a critical role in chromosome condensation and separation through the polyubiquitination of securin. Autoantibodies against the encoded protein may be markers for scleroderma and Crohn's disease. A pseudogene of this gene is located on the long arm of chromosome 3. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2011]

UBE4A links:

LOC100131626 (HGNC:):

LOC100131626 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
UBE4A	NM_001204077.2 link	c.2412+14_2412+23delAAAAAAAAAA	intron_variant	Intron 15 of 19	ENST00000252108.8	NP_001191006.1
UBE4A	NM_004788.4 link	c.2433+14_2433+23delAAAAAAAAAA	intron_variant	Intron 15 of 19		NP_004779.2
LOC100131626	NR_046369.1 link	n.232-3397_232-3388delTTTTTTTTTT	intron_variant	Intron 3 of 3
LOC100131626	NR_046370.1 link	n.232-3450_232-3441delTTTTTTTTTT	intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
UBE4A	ENST00000252108.8 link	c.2412+3_2412+12delAAAAAAAAAA	splice_region_variant, intron_variant	Intron 15 of 19	1	NM_001204077.2	ENSP00000252108.4	Q14139-1
UBE4A	ENST00000431736.6 link	c.2433+3_2433+12delAAAAAAAAAA	splice_region_variant, intron_variant	Intron 15 of 19	1		ENSP00000387362.2	Q14139-2
UBE4A	ENST00000545354.1 link	c.828+3_828+12delAAAAAAAAAA	splice_region_variant, intron_variant	Intron 6 of 10	2		ENSP00000438918.1	B7Z7P0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000101

AC:

AN:

987620

Hom.:

AF XY:

0.00

AC XY:

AN XY:

503542

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000136

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

No publications associated with this variant yet.

11-118384947-TAAAAAAAAAAAAA-TAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over