chr11-118384947-T-TAAAAAAAAA

Variant names:

• chr11-118384947-T-TAAAAAAAAA
• rs370025001
• NM_001204077.2:c.2412+15_2412+23dupAAAAAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000252108.8(UBE4A):​c.2412+2_2412+3insAAAAAAAAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000126 in 79,514 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: 𝑓 0.000013 (0 hom., cov: 29)
• Consequence: UBE4A ENST00000252108.8 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.09
• Publications: 0 publications found

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

LOC100131626 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE4A	NM_001204077.2	MANE Select	c.2412+15_2412+23dupAAAAAAAAA		intron	N/A	NP_001191006.1	Q14139-1
	UBE4A	NM_004788.4		c.2433+15_2433+23dupAAAAAAAAA		intron	N/A	NP_004779.2
	LOC100131626	NR_046369.1		n.232-3396_232-3388dupTTTTTTTTT		intron	N/A

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.0000126 AC: 1 AN: 79514 Hom.: 0 Cov.: 29

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: 0.0000267

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.0000126 AC: 1 AN: 79514 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 37764

African (AFR) AF: 0.00 AC: 0 AN: 21848

American (AMR) AF: 0.00 AC: 0 AN: 6906

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2000

East Asian (EAS) AF: 0.00 AC: 0 AN: 2948

South Asian (SAS) AF: 0.00 AC: 0 AN: 2578

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4192

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 130

European-Non Finnish (NFE) AF: 0.0000267 AC: 1 AN: 37442

Other (OTH) AF: 0.00 AC: 0 AN: 1018

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

Other links and lift over

dbSNP: rs370025001; hg19: chr11-118255662;