chr11-118384947-T-TAAAAAAAAAAAAAAAAAAAAAAAATAAAAAAAAAAAAAAAAAAA

Variant names:

• chr11-118384947-T-TAAAAAAAAAAAAAAAAAAAAAAAATAAAAAAAAAAAAAAAAAAA
• rs370025001
• NM_001204077.2:c.2412+23_2412+24insAAATAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA

Variant summary

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

The NM_001204077.2(UBE4A):​c.2412+23_2412+24insAAATAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 29)
• Consequence: UBE4A NM_001204077.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.09
• Publications: 1 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 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE4A	NM_001204077.2	c.2412+23_2412+24insAAATAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA		intron_variant	Intron 15 of 19	ENST00000252108.8	NP_001191006.1
UBE4A	NM_004788.4	c.2433+23_2433+24insAAATAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA		intron_variant	Intron 15 of 19		NP_004779.2
LOC100131626	NR_046369.1	n.232-3388_232-3387insTTTTTTTTTTTTTTTTTTTATTTTTTTTTTTTTTTTTTTTTTTT		intron_variant	Intron 3 of 3
LOC100131626	NR_046370.1	n.232-3441_232-3440insTTTTTTTTTTTTTTTTTTTATTTTTTTTTTTTTTTTTTTTTTTT		intron_variant	Intron 3 of 3

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 29

Alfa AF: 0.0000601 Hom.: 14

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

Other links and lift over

dbSNP: rs370025001; hg19: chr11-118255662;