2-55636238-C-A
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_033109.5(PNPT1):c.2351G>T(p.Ter784Leuext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
PNPT1
NM_033109.5 stop_lost
NM_033109.5 stop_lost
Scores
2
5
Clinical Significance
Conservation
PhyloP100: 1.99
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]
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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
Stoplost variant in NM_033109.5 Downstream stopcodon found after 51 codons.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PNPT1 | NM_033109.5 | c.2351G>T | p.Ter784Leuext*? | stop_lost | 28/28 | ENST00000447944.7 | NP_149100.2 | |
PNPT1 | XM_005264629.3 | c.2111G>T | p.Ter704Leuext*? | stop_lost | 28/28 | XP_005264686.1 | ||
PNPT1 | XM_017005172.2 | c.2111G>T | p.Ter704Leuext*? | stop_lost | 27/27 | XP_016860661.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PNPT1 | ENST00000447944.7 | c.2351G>T | p.Ter784Leuext*? | stop_lost | 28/28 | 1 | NM_033109.5 | ENSP00000400646.2 | ||
PNPT1 | ENST00000260604.8 | n.*1893G>T | non_coding_transcript_exon_variant | 27/27 | 5 | ENSP00000260604.4 | ||||
PNPT1 | ENST00000415374.5 | n.2351G>T | non_coding_transcript_exon_variant | 28/29 | 5 | ENSP00000393953.1 | ||||
PNPT1 | ENST00000260604.8 | n.*1893G>T | 3_prime_UTR_variant | 27/27 | 5 | ENSP00000260604.4 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1423186Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 707178
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1423186
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
707178
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
Bravo
AF:
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 | GeneDx | Dec 08, 2023 | Stop codon loss and change to a Leu codon, leading to protein extension and the addition of 14 amino acids at the C-terminus; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
Vest4
GERP RS
Splicing
Name
Calibrated prediction
Score
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at