chr16-89709819-G-A
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_004913.3(VPS9D1):c.1346C>T(p.Pro449Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,613,608 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
VPS9D1
NM_004913.3 missense
NM_004913.3 missense
Scores
5
14
Clinical Significance
Conservation
PhyloP100: 4.03
Genes affected
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.31712607).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
VPS9D1 | NM_004913.3 | c.1346C>T | p.Pro449Leu | missense_variant | 11/15 | ENST00000389386.8 | NP_004904.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
VPS9D1 | ENST00000389386.8 | c.1346C>T | p.Pro449Leu | missense_variant | 11/15 | 1 | NM_004913.3 | ENSP00000374037 | A2 | |
VPS9D1 | ENST00000561976.5 | c.1136C>T | p.Pro379Leu | missense_variant | 10/14 | 1 | ENSP00000454244 | P2 | ||
VPS9D1 | ENST00000565023.1 | c.149C>T | p.Pro50Leu | missense_variant | 2/6 | 5 | ENSP00000455792 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152042Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
2
AN:
152042
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461566Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727118
GnomAD4 exome
AF:
AC:
3
AN:
1461566
Hom.:
Cov.:
31
AF XY:
AC XY:
2
AN XY:
727118
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000132 AC: 2AN: 152042Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74272
GnomAD4 genome
AF:
AC:
2
AN:
152042
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74272
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
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 | Nov 22, 2021 | The c.1346C>T (p.P449L) alteration is located in exon 11 (coding exon 11) of the VPS9D1 gene. This alteration results from a C to T substitution at nucleotide position 1346, causing the proline (P) at amino acid position 449 to be replaced by a leucine (L). 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
Uncertain
DANN
Benign
DEOGEN2
Benign
.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Uncertain
D;D
Polyphen
0.0030
.;B
Vest4
MutPred
0.49
.;Gain of helix (P = 0.0199);
MVP
MPC
0.18
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at