rs587784317
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_006031.6(PCNT):c.6922-4A>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000845 in 1,538,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_006031.6 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCNT | NM_006031.6 | c.6922-4A>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000359568.10 | |||
PCNT | NM_001315529.2 | c.6568-4A>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCNT | ENST00000359568.10 | c.6922-4A>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_006031.6 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000503 AC: 7AN: 139100Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000804 AC: 2AN: 248684Hom.: 0 AF XY: 0.00000742 AC XY: 1AN XY: 134688
GnomAD4 exome AF: 0.00000429 AC: 6AN: 1399848Hom.: 0 Cov.: 25 AF XY: 0.00000428 AC XY: 3AN XY: 700550
GnomAD4 genome ? AF: 0.0000503 AC: 7AN: 139100Hom.: 0 Cov.: 33 AF XY: 0.0000588 AC XY: 4AN XY: 68008
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 29, 2022 | This sequence change falls in intron 30 of the PCNT gene. It does not directly change the encoded amino acid sequence of the PCNT protein. This variant is present in population databases (no rsID available, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with PCNT-related conditions. ClinVar contains an entry for this variant (Variation ID: 1309261). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Nov 07, 2019 | Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown. - |
PCNT-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 28, 2023 | The PCNT c.6922-4A>G variant is predicted to interfere with splicing. This variant is predicted to alter splicing based on available splicing prediction programs (Alamut Visual Plus v1.6.1). However, the use of computer prediction programs is not equivalent to functional evidence. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0058% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at