chr16-89709365-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004913.3(VPS9D1):c.1459G>A(p.Ala487Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000953 in 1,573,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000099 ( 0 hom. )
Consequence
VPS9D1
NM_004913.3 missense
NM_004913.3 missense
Scores
2
17
Clinical Significance
Conservation
PhyloP100: 3.98
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16996557).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
VPS9D1 | NM_004913.3 | c.1459G>A | p.Ala487Thr | missense_variant | 12/15 | ENST00000389386.8 | NP_004904.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
VPS9D1 | ENST00000389386.8 | c.1459G>A | p.Ala487Thr | missense_variant | 12/15 | 1 | NM_004913.3 | ENSP00000374037 | A2 | |
VPS9D1 | ENST00000561976.5 | c.1249G>A | p.Ala417Thr | missense_variant | 11/14 | 1 | ENSP00000454244 | P2 | ||
VPS9D1 | ENST00000565023.1 | c.262G>A | p.Ala88Thr | missense_variant | 3/6 | 5 | ENSP00000455792 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151960Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000192 AC: 4AN: 208714Hom.: 0 AF XY: 0.0000177 AC XY: 2AN XY: 113218
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GnomAD4 exome AF: 0.00000985 AC: 14AN: 1421204Hom.: 0 Cov.: 32 AF XY: 0.0000142 AC XY: 10AN XY: 704306
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GnomAD4 genome AF: 0.00000658 AC: 1AN: 151960Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74198
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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 | Aug 26, 2022 | The c.1459G>A (p.A487T) alteration is located in exon 12 (coding exon 12) of the VPS9D1 gene. This alteration results from a G to A substitution at nucleotide position 1459, causing the alanine (A) at amino acid position 487 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M
MutationTaster
Benign
D;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
0.55
.;P
Vest4
MVP
MPC
0.23
ClinPred
T
GERP RS
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