Genetic Variant NM_001204077.2:c.2412+11_2412+23delAAAAAAAAAAAAA (chr11-118384947-TAAAAAAAAAAAAA-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001204077.2(UBE4A):c.2412+11_2412+23delAAAAAAAAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 1,067,142 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_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 0.000038 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

UBE4A
NM_001204077.2 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
UBE4A	NM_001204077.2 link	c.2412+11_2412+23delAAAAAAAAAAAAA	intron_variant	Intron 15 of 19	ENST00000252108.8	NP_001191006.1
UBE4A	NM_004788.4 link	c.2433+11_2433+23delAAAAAAAAAAAAA	intron_variant	Intron 15 of 19		NP_004779.2
LOC100131626	NR_046369.1 link	n.232-3400_232-3388delTTTTTTTTTTTTT	intron_variant	Intron 3 of 3
LOC100131626	NR_046370.1 link	n.232-3453_232-3441delTTTTTTTTTTTTT	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+15delAAAAAAAAAAAAA	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+15delAAAAAAAAAAAAA	splice_region_variant, intron_variant	Intron 15 of 19	1		ENSP00000387362.2	Q14139-2
UBE4A	ENST00000545354.1 link	c.828+3_828+15delAAAAAAAAAAAAA	splice_region_variant, intron_variant	Intron 6 of 10	2		ENSP00000438918.1	B7Z7P0

Frequencies

GnomAD3 genomes

AF:

0.0000377

AC:

AN:

79516

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000915

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:

0.0000267

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000132

AC:

AN:

987626

Hom.:

AF XY:

0.0000199

AC XY:

AN XY:

503546

show subpopulations

African (AFR)

AF:

0.0000899

AC:

AN:

22242

American (AMR)

AF:

0.00

AC:

AN:

28600

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18950

East Asian (EAS)

AF:

0.00

AC:

AN:

34804

South Asian (SAS)

AF:

0.00

AC:

AN:

63528

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34472

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3898

European-Non Finnish (NFE)

AF:

0.0000136

AC:

AN:

738006

Other (OTH)

AF:

0.0000232

AC:

AN:

43126

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.671

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.0000377

AC:

AN:

79516

Hom.:

Cov.:

AF XY:

0.0000265

AC XY:

AN XY:

37764

show subpopulations

African (AFR)

AF:

0.0000915

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:

0.0000267

AC:

AN:

37442

Other (OTH)

AF:

0.00

AC:

AN:

1018

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.1

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over