rs869025320
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001371986.1(UNC80):c.151C>T(p.Arg51Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,352 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
NM_001371986.1 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 | UniProt |
---|---|---|---|---|---|---|---|
UNC80 | NM_001371986.1 | c.151C>T | p.Arg51Ter | stop_gained | 3/65 | ENST00000673920.1 | |
UNC80 | NM_032504.2 | c.151C>T | p.Arg51Ter | stop_gained | 3/64 | ||
UNC80 | NM_182587.4 | c.151C>T | p.Arg51Ter | stop_gained | 3/63 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UNC80 | ENST00000673920.1 | c.151C>T | p.Arg51Ter | stop_gained | 3/65 | NM_001371986.1 | A2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461352Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 726956
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Hypotonia, infantile, with psychomotor retardation and characteristic facies 2 Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 14, 2016 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Dec 02, 2022 | Variant summary: UNC80 c.151C>T (p.Arg51X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic in ClinVar and HGMD. The variant was absent in 251190 control chromosomes. c.151C>T has been reported in the literature in multiple homozygous individuals of a remotely related consanguineous Bedouin kindred, affected with Infantile Hypotonia With Psychomotor Retardation And Characteristic Facies 2 (Perez_2016). These data indicate that the variant is very likely to be associated with disease. Experimental evidence evaluating an impact on protein function, demonstrated the variant protein was not expressed in vitro (Perez_2016). A ClinVar submitter (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at