19-40394015-CCT-C
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The NM_181882.3(PRX):c.4335_4336del(p.Ala1447SerfsTer40) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,538 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. T1445T) has been classified as Likely benign.
Frequency
Consequence
NM_181882.3 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRX | NM_181882.3 | c.4335_4336del | p.Ala1447SerfsTer40 | frameshift_variant | 7/7 | ENST00000324001.8 | |
PRX | NM_001411127.1 | c.4620_4621del | p.Ala1542SerfsTer40 | frameshift_variant | 7/7 | ||
PRX | XM_017027047.2 | c.4233_4234del | p.Ala1413SerfsTer40 | frameshift_variant | 4/4 | ||
PRX | NM_020956.2 | c.*4540_*4541del | 3_prime_UTR_variant | 6/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRX | ENST00000324001.8 | c.4335_4336del | p.Ala1447SerfsTer40 | frameshift_variant | 7/7 | 1 | NM_181882.3 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152226Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250340Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135532
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461312Hom.: 0 AF XY: 0.00000688 AC XY: 5AN XY: 726948
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152226Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74366
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Molecular Genetics Laboratory, London Health Sciences Centre | - | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 24, 2019 | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge - |
Charcot-Marie-Tooth disease type 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 24, 2020 | This sequence change results in a premature translational stop signal in the PRX gene (p.Ala1447Serfs*40). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 15 amino acids of the PRX protein and extend the protein by an additional 24 amino acids. This variant is present in population databases (rs778270475, ExAC 0.003%). This variant has not been reported in the literature in individuals with PRX-related conditions. 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:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at