rs1554643142
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_078480.3(PUF60):c.619_637del(p.Asn207ProfsTer3) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
PUF60
NM_078480.3 frameshift
NM_078480.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.30
Genes affected
PUF60 (HGNC:17042): (poly(U) binding splicing factor 60) This gene encodes a nucleic acid-binding protein that plays a role in a variety of nuclear processes, including pre-mRNA splicing and transcriptional regulation. The encoded protein forms a complex with the far upstream DNA element (FUSE) and FUSE-binding protein at the myelocytomatosis oncogene (MYC) promoter. This complex represses MYC transcription through the core-TFIIH basal transcription factor. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2012]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 8-143818041-GGCTGGGCCTGCCCTATGTT-G is Pathogenic according to our data. Variant chr8-143818041-GGCTGGGCCTGCCCTATGTT-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 425573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-143818041-GGCTGGGCCTGCCCTATGTT-G is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PUF60 | NM_078480.3 | c.619_637del | p.Asn207ProfsTer3 | frameshift_variant | 8/12 | ENST00000526683.6 | NP_510965.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PUF60 | ENST00000526683.6 | c.619_637del | p.Asn207ProfsTer3 | frameshift_variant | 8/12 | 1 | NM_078480.3 | ENSP00000434359 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Pathogenic:2
Likely pathogenic, criteria provided, single submitter | research | Bristol Genetics Laboratory, North Bristol NHS Trust | Jan 19, 2017 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Apr 05, 2024 | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 28327570, 27535533) - |
8q24.3 microdeletion syndrome Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University of Leipzig Medical Center | Jun 01, 2016 | This variant was identified as de novo (maternity and paternity confirmed). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at