chrX-53562114-A-ATCATCTTCC

Position:

• chrX-53562114-A-ATCATCTTCC

Variant summary

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

The ENST00000262854.11(HUWE1):​c.7334_7335insGGAAGATGA​(p.Glu2442_Asp2444dup) variant causes a inframe insertion change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 22)
• Consequence: HUWE1 ENST00000262854.11 inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.78

Genes affected

HUWE1 (HGNC:30892): (HECT, UBA and WWE domain containing E3 ubiquitin protein ligase 1) This gene encodes a protein containing a C-terminal HECT (E6AP type E3 ubiquitin protein ligase) domain that functions as an E3 ubiquitin ligase. The encoded protein is required for the ubiquitination and subsequent degradation of the anti-apoptotic protein Mcl1 (myeloid cell leukemia sequence 1 (BCL2-related)). This protein also ubiquitinates the p53 tumor suppressor, core histones, and DNA polymerase beta. Mutations in this gene are associated with Turner type X-linked syndromic cognitive disability. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HUWE1	NM_031407.7	c.7334_7335insGGAAGATGA	p.Glu2442_Asp2444dup	inframe_insertion	54/84	ENST00000262854.11	NP_113584.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HUWE1	ENST00000262854.11	c.7334_7335insGGAAGATGA	p.Glu2442_Asp2444dup	inframe_insertion	54/84	1	NM_031407.7	ENSP00000262854	P2
HUWE1	ENST00000342160.7	c.7334_7335insGGAAGATGA	p.Glu2442_Asp2444dup	inframe_insertion	53/83	5		ENSP00000340648	P2
HUWE1	ENST00000612484.4	c.7307_7308insGGAAGATGA	p.Glu2433_Asp2435dup	inframe_insertion	51/81	5		ENSP00000479451	A2
HUWE1	ENST00000704099.1	c.7331_7332insGGAAGATGA	p.Glu2441_Asp2443dup	inframe_insertion	53/83			ENSP00000515693

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 22

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs781889045; hg19: chrX-53589075;