rs879012592
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate
The NM_031483.7(ITCH):c.966-9C>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00033 ( 0 hom., cov: 0)
Exomes 𝑓: 0.010 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
ITCH
NM_031483.7 splice_polypyrimidine_tract, intron
NM_031483.7 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.0005665
2
Clinical Significance
Conservation
PhyloP100: -0.212
Genes affected
ITCH (HGNC:13890): (itchy E3 ubiquitin protein ligase) This gene encodes a member of the Nedd4 family of HECT domain E3 ubiquitin ligases. HECT domain E3 ubiquitin ligases transfer ubiquitin from E2 ubiquitin-conjugating enzymes to protein substrates, thus targeting specific proteins for lysosomal degradation. The encoded protein plays a role in multiple cellular processes including erythroid and lymphoid cell differentiation and the regulation of immune responses. Mutations in this gene are a cause of syndromic multisystem autoimmune disease. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Mar 2012]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 20-34445278-C-A is Benign according to our data. Variant chr20-34445278-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1114807.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-34445278-C-A is described in Lovd as [Likely_benign].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ITCH | NM_031483.7 | c.966-9C>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000374864.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ITCH | ENST00000374864.10 | c.966-9C>A | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_031483.7 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 15AN: 45120Hom.: 0 Cov.: 0 FAILED QC
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0104 AC: 5980AN: 577742Hom.: 0 Cov.: 32 AF XY: 0.0101 AC XY: 2925AN XY: 289080
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GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.000332 AC: 15AN: 45162Hom.: 0 Cov.: 0 AF XY: 0.000413 AC XY: 9AN XY: 21788
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Data not reliable, filtered out with message: AS_VQSR
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Syndromic multisystem autoimmune disease due to ITCH deficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 21, 2020 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at