11-65096282-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_013265.4(VPS51):c.32C>T(p.Pro11Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000691 in 1,519,474 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_013265.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152162Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000136 AC: 15AN: 110116Hom.: 0 AF XY: 0.000129 AC XY: 8AN XY: 61930
GnomAD4 exome AF: 0.0000666 AC: 91AN: 1367194Hom.: 0 Cov.: 32 AF XY: 0.0000666 AC XY: 45AN XY: 675426
GnomAD4 genome AF: 0.0000919 AC: 14AN: 152280Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74446
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.32C>T (p.P11L) alteration is located in exon 1 (coding exon 1) of the VPS51 gene. This alteration results from a C to T substitution at nucleotide position 32, causing the proline (P) at amino acid position 11 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Pontocerebellar hypoplasia, type 13 Uncertain:1
This sequence variant is a single nucleotide substitution (C>T) at position 32 of the coding sequence of the VPS51 gene that results in a proline to leucine amino acid change at residue 11 of the VPS51 subunit of GARP complex protein. This is a previously reported variant (ClinVar 2366203) that has not been observed in individuals affected by a VPS51-related disorder in the published literature, to our knowledge. This variant is present in 105 of 1519474 alleles (0.0069%) in the gnomAD v4.1.0 population dataset. Multiple bioinformatic tools predict that this amino acid change would be neutral, and the Pro11 residue at this position is poorly conserved across the vertebrate species examined. Studies examining the functional consequence of this variant have not been published, to our knowledge. At this time, there is insufficient evidence to determine if this variant is pathogenic or benign. Therefore, we consider this a variant of uncertain significance. ACMG Criteria: BP4 -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at