Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001114394.3(TENT2):c.1069C>A(p.Pro357Thr) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000712 in 1,586,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
TENT2 (HGNC:26776): (terminal nucleotidyltransferase 2) Enables 5'-3' RNA polymerase activity and polynucleotide adenylyltransferase activity. Involved in RNA metabolic process and negative regulation of RNA catabolic process. Predicted to be located in nucleus. Predicted to be part of nuclear RNA-directed RNA polymerase complex. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (MetaRNN=0.120901704).
Uncertain significance, criteria provided, single submitter
clinical testing
Ambry Genetics
Nov 06, 2023
The c.1069C>A (p.P357T) alteration is located in exon 11 (coding exon 10) of the PAPD4 gene. This alteration results from a C to A substitution at nucleotide position 1069, causing the proline (P) at amino acid position 357 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -