17-42773498-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 5P and 4B. PM5PP3_ModeratePP5BS2
The NM_032353.4(VPS25):c.23C>T(p.Pro8Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,614,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P8S) has been classified as Likely pathogenic.
Frequency
Consequence
NM_032353.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
VPS25 | NM_032353.4 | c.23C>T | p.Pro8Leu | missense_variant | Exon 1 of 6 | ENST00000253794.7 | NP_115729.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152134Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251494Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135922
GnomAD4 exome AF: 0.0000171 AC: 25AN: 1461892Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 727246
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152252Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74452
ClinVar
Submissions by phenotype
VPS25-related neurodevelopmental delay Pathogenic:1
- -
not specified Uncertain:1
The c.23C>T (p.P8L) alteration is located in exon 1 (coding exon 1) of the VPS25 gene. This alteration results from a C to T substitution at nucleotide position 23, causing the proline (P) at amino acid position 8 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at