15-50462296-A-G
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_005154.5(USP8):āc.515A>Gā(p.Asn172Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000109 in 1,603,156 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
USP8 | NM_005154.5 | c.515A>G | p.Asn172Ser | missense_variant | 6/20 | ENST00000307179.9 | NP_005145.3 | |
USP8 | NM_001128610.3 | c.515A>G | p.Asn172Ser | missense_variant | 6/20 | NP_001122082.1 | ||
USP8 | NM_001283049.2 | c.284A>G | p.Asn95Ser | missense_variant | 4/17 | NP_001269978.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
USP8 | ENST00000307179.9 | c.515A>G | p.Asn172Ser | missense_variant | 6/20 | 1 | NM_005154.5 | ENSP00000302239 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152210Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000667 AC: 16AN: 239880Hom.: 0 AF XY: 0.0000540 AC XY: 7AN XY: 129658
GnomAD4 exome AF: 0.000118 AC: 171AN: 1450946Hom.: 0 Cov.: 31 AF XY: 0.000109 AC XY: 79AN XY: 721576
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152210Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74364
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 01, 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with USP8-related conditions. This variant is present in population databases (rs147121994, gnomAD 0.01%). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 172 of the USP8 protein (p.Asn172Ser). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at