16-89708452-C-A
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The ENST00000389386.8(VPS9D1):c.1777G>T(p.Ala593Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000118 in 1,612,536 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
VPS9D1
ENST00000389386.8 missense
ENST00000389386.8 missense
Scores
3
7
9
Clinical Significance
Conservation
PhyloP100: 5.71
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.795
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
VPS9D1 | NM_004913.3 | c.1777G>T | p.Ala593Ser | missense_variant | 14/15 | ENST00000389386.8 | NP_004904.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
VPS9D1 | ENST00000389386.8 | c.1777G>T | p.Ala593Ser | missense_variant | 14/15 | 1 | NM_004913.3 | ENSP00000374037 | A2 | |
VPS9D1 | ENST00000561976.5 | c.1567G>T | p.Ala523Ser | missense_variant | 13/14 | 1 | ENSP00000454244 | P2 | ||
VPS9D1 | ENST00000565023.1 | c.580G>T | p.Ala194Ser | missense_variant | 5/6 | 5 | ENSP00000455792 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152244Hom.: 0 Cov.: 34
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GnomAD4 exome AF: 0.0000123 AC: 18AN: 1460292Hom.: 0 Cov.: 32 AF XY: 0.00000826 AC XY: 6AN XY: 726438
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152244Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1AN XY: 74374
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 06, 2022 | The c.1777G>T (p.A593S) alteration is located in exon 14 (coding exon 14) of the VPS9D1 gene. This alteration results from a G to T substitution at nucleotide position 1777, causing the alanine (A) at amino acid position 593 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
.;M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Uncertain
D;D
Polyphen
1.0
.;D
Vest4
MutPred
0.58
.;Gain of relative solvent accessibility (P = 0.0479);
MVP
MPC
0.68
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at