rs768800460
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_005154.5(USP8):āc.1084A>Gā(p.Ile362Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000212 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_005154.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USP8 | NM_005154.5 | c.1084A>G | p.Ile362Val | missense_variant | 10/20 | ENST00000307179.9 | |
USP8 | NM_001128610.3 | c.1084A>G | p.Ile362Val | missense_variant | 10/20 | ||
USP8 | NM_001283049.2 | c.853A>G | p.Ile285Val | missense_variant | 8/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USP8 | ENST00000307179.9 | c.1084A>G | p.Ile362Val | missense_variant | 10/20 | 1 | NM_005154.5 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251206Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135820
GnomAD4 exome AF: 0.0000212 AC: 31AN: 1461864Hom.: 0 Cov.: 31 AF XY: 0.0000303 AC XY: 22AN XY: 727228
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 13, 2022 | ClinVar contains an entry for this variant (Variation ID: 458311). This variant has not been reported in the literature in individuals affected with USP8-related conditions. This variant is present in population databases (rs768800460, gnomAD 0.02%). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 362 of the USP8 protein (p.Ile362Val). 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at