rs773997755
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_031483.7(ITCH):āc.694T>Gā(p.Ser232Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_031483.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ITCH | NM_031483.7 | c.694T>G | p.Ser232Ala | missense_variant | 9/25 | ENST00000374864.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ITCH | ENST00000374864.10 | c.694T>G | p.Ser232Ala | missense_variant | 9/25 | 1 | NM_031483.7 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251286Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135820
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1460114Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 726498
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Syndromic multisystem autoimmune disease due to ITCH deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 12, 2022 | This sequence change replaces serine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 232 of the ITCH protein (p.Ser232Ala). This variant is present in population databases (rs773997755, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with ITCH-related conditions. ClinVar contains an entry for this variant (Variation ID: 538752). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at