rs1555498129
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The ENST00000219281.8(USB1):c.415C>T(p.Gln139Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
ENST00000219281.8 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
USB1 | NM_024598.4 | c.415C>T | p.Gln139Ter | stop_gained | 3/7 | ENST00000219281.8 | NP_078874.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
USB1 | ENST00000219281.8 | c.415C>T | p.Gln139Ter | stop_gained | 3/7 | 1 | NM_024598.4 | ENSP00000219281 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461866Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727232
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 19, 2023 | This sequence change creates a premature translational stop signal (p.Gln139*) in the USB1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in USB1 are known to be pathogenic (PMID: 20817924, 25044170). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with poikiloderma with neutropenia (PMID: 21271650). ClinVar contains an entry for this variant (Variation ID: 496757). For these reasons, this variant has been classified as Pathogenic. - |
Poikiloderma with neutropenia Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at