chr15-50498636-T-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_005154.5(USP8):c.3079T>A(p.Ser1027Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,612,644 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 (★).
Frequency
Consequence
NM_005154.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USP8 | NM_005154.5 | c.3079T>A | p.Ser1027Thr | missense_variant | 19/20 | ENST00000307179.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USP8 | ENST00000307179.9 | c.3079T>A | p.Ser1027Thr | missense_variant | 19/20 | 1 | NM_005154.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152200Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000279 AC: 7AN: 250850Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135570
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1460326Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 726366
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152318Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74484
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 04, 2022 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with USP8-related conditions. This variant is present in population databases (rs770957779, gnomAD 0.03%). This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 1027 of the USP8 protein (p.Ser1027Thr). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at