Genetic Variant UBE4A:c.2412+3_2412+23dupAAAAAAAAAAAAAAAAAAAAA (chr11-118384947-T-TAAAAAAAAAAAAAAAAAAAAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000252108.8(UBE4A):c.2412+2_2412+3insAAAAAAAAAAAAAAAAAAAAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 29)

Failed GnomAD Quality Control

Consequence

UBE4A
ENST00000252108.8 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.09

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with hypotonia and gross motor and speech delay
Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
autosomal recessive non-syndromic intellectual disability
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
multiple congenital anomalies/dysmorphic syndrome
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

UBE4A links:

LOC100131626 (HGNC:):

LOC100131626 links:

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new If you want to explore the variant's impact on the transcript ENST00000252108.8, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000252108.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
UBE4A	NM_001204077.2	MANE Select	c.2412+3_2412+23dupAAAAAAAAAAAAAAAAAAAAA	intron	N/A	NP_001191006.1	Q14139-1
UBE4A	NM_004788.4		c.2433+3_2433+23dupAAAAAAAAAAAAAAAAAAAAA	intron	N/A	NP_004779.2
LOC100131626	NR_046369.1		n.232-3408_232-3388dupTTTTTTTTTTTTTTTTTTTTT	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
UBE4A	ENST00000252108.8	TSL:1 MANE Select	c.2412+2_2412+3insAAAAAAAAAAAAAAAAAAAAA	splice_region intron	N/A	ENSP00000252108.4	Q14139-1
UBE4A	ENST00000431736.6	TSL:1	c.2433+2_2433+3insAAAAAAAAAAAAAAAAAAAAA	splice_region intron	N/A	ENSP00000387362.2	Q14139-2
UBE4A	ENST00000911347.1		c.2430+2_2430+3insAAAAAAAAAAAAAAAAAAAAA	splice_region intron	N/A	ENSP00000581406.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

79516

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

79516

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

37764

African (AFR)

AF:

0.00

AC:

AN:

21850

American (AMR)

AF:

0.00

AC:

AN:

6906

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2000

East Asian (EAS)

AF:

0.00

AC:

AN:

2948

South Asian (SAS)

AF:

0.00

AC:

AN:

2578

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4192

Middle Eastern (MID)

AF:

0.00

AC:

AN:

130

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

37442

Other (OTH)

AF:

0.00

AC:

AN:

1018

Alfa

AF:

0.000180

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.1

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over