chr16-89708878-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_004913.3(VPS9D1):c.1676C>T(p.Pro559Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000139 in 1,584,140 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_004913.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
VPS9D1 | NM_004913.3 | c.1676C>T | p.Pro559Leu | missense_variant | 13/15 | ENST00000389386.8 | NP_004904.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
VPS9D1 | ENST00000389386.8 | c.1676C>T | p.Pro559Leu | missense_variant | 13/15 | 1 | NM_004913.3 | ENSP00000374037 | A2 | |
VPS9D1 | ENST00000561976.5 | c.1466C>T | p.Pro489Leu | missense_variant | 12/14 | 1 | ENSP00000454244 | P2 | ||
VPS9D1 | ENST00000565023.1 | c.479C>T | p.Pro160Leu | missense_variant | 4/6 | 5 | ENSP00000455792 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152184Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.00000967 AC: 2AN: 206852Hom.: 0 AF XY: 0.00000873 AC XY: 1AN XY: 114612
GnomAD4 exome AF: 0.0000119 AC: 17AN: 1431956Hom.: 0 Cov.: 33 AF XY: 0.0000140 AC XY: 10AN XY: 711882
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152184Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2AN XY: 74342
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 12, 2023 | The c.1676C>T (p.P559L) alteration is located in exon 13 (coding exon 13) of the VPS9D1 gene. This alteration results from a C to T substitution at nucleotide position 1676, causing the proline (P) at amino acid position 559 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