chr2-55636240-CT-C
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_033109.5(PNPT1):c.2348del(p.Gln783ArgfsTer6) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. Q783Q) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 33)
Consequence
PNPT1
NM_033109.5 frameshift
NM_033109.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.509
Genes affected
PNPT1 (HGNC:23166): (polyribonucleotide nucleotidyltransferase 1) The protein encoded by this gene belongs to the evolutionary conserved polynucleotide phosphorylase family comprised of phosphate dependent 3'-to-5' exoribonucleases implicated in RNA processing and degradation. This enzyme is predominantly localized in the mitochondrial intermembrane space and is involved in import of RNA to mitochondria. Mutations in this gene have been associated with combined oxidative phosphorylation deficiency-13 and autosomal recessive nonsyndromic deafness-70. Related pseudogenes are found on chromosomes 3 and 7. [provided by RefSeq, Dec 2012]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Frameshift in the end of transcript resulting in stoplost. Downstream stopcodon found after 783 codons.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PNPT1 | NM_033109.5 | c.2348del | p.Gln783ArgfsTer6 | frameshift_variant | 28/28 | ENST00000447944.7 | |
PNPT1 | XM_005264629.3 | c.2108del | p.Gln703ArgfsTer6 | frameshift_variant | 28/28 | ||
PNPT1 | XM_017005172.2 | c.2108del | p.Gln703ArgfsTer6 | frameshift_variant | 27/27 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PNPT1 | ENST00000447944.7 | c.2348del | p.Gln783ArgfsTer6 | frameshift_variant | 28/28 | 1 | NM_033109.5 | P1 | |
PNPT1 | ENST00000415374.5 | c.2348del | p.Gln783ArgfsTer6 | frameshift_variant, NMD_transcript_variant | 28/29 | 5 | |||
PNPT1 | ENST00000260604.8 | c.*1890del | 3_prime_UTR_variant, NMD_transcript_variant | 27/27 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 12, 2022 | ClinVar contains an entry for this variant (Variation ID: 1476883). This variant has not been reported in the literature in individuals affected with PNPT1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change results in a frameshift in the PNPT1 gene (p.Gln783Argfs*6). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1 amino acid(s) of the PNPT1 protein and extend the protein by 4 additional amino acid residues. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at