chrX-48902788-G-GCCCC
Position:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_001032382.2(PQBP1):c.637_640dup(p.Arg214ProfsTer14) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 21)
Consequence
PQBP1
NM_001032382.2 frameshift
NM_001032382.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.81
Genes affected
PQBP1 (HGNC:9330): (polyglutamine binding protein 1) This gene encodes a nuclear polyglutamine-binding protein that is involved with transcription activation. The encoded protein contains a WW domain. Mutations in this gene have been found in patients with Renpenning syndrome 1 and other syndromes with X-linked cognitive disability. Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene.[provided by RefSeq, Nov 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. There are 6 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant X-48902788-G-GCCCC is Pathogenic according to our data. Variant chrX-48902788-G-GCCCC is described in ClinVar as [Likely_pathogenic]. Clinvar id is 422848.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PQBP1 | NM_001032382.2 | c.637_640dup | p.Arg214ProfsTer14 | frameshift_variant | 6/7 | ENST00000447146.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PQBP1 | ENST00000447146.7 | c.637_640dup | p.Arg214ProfsTer14 | frameshift_variant | 6/7 | 1 | NM_001032382.2 | P1 |
Frequencies
GnomAD3 genomes Cov.: 21
GnomAD3 genomes
Cov.:
21
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome Cov.: 21
GnomAD4 genome
Cov.:
21
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Dec 01, 2017 | The c.637_640dupCCCC variant in the PQBP1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.637_640dupCCCC variant causes a frameshift starting with codon Arginine 214, changes this amino acid to a Proline residue, and creates a premature Stop codon at position 14 of the new reading frame, denoted p.Arg214ProfsX14. This variant is predicted to cause loss of normal protein function through protein truncation. The c.637_640dupCCCC variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.637_640dupCCCC as a likely pathogenic variant. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at