chr16-89709254-A-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_004913.3(VPS9D1):āc.1570T>Cā(p.Cys524Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000726 in 1,459,618 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 (ā ).
Frequency
Genomes: not found (cov: 31)
Exomes š: 0.000073 ( 0 hom. )
Consequence
VPS9D1
NM_004913.3 missense
NM_004913.3 missense
Scores
5
9
5
Clinical Significance
Conservation
PhyloP100: 6.23
Genes affected
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.888
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
VPS9D1 | NM_004913.3 | c.1570T>C | p.Cys524Arg | 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.1570T>C | p.Cys524Arg | missense_variant | 12/15 | 1 | NM_004913.3 | ENSP00000374037 | A2 | |
VPS9D1 | ENST00000561976.5 | c.1360T>C | p.Cys454Arg | missense_variant | 11/14 | 1 | ENSP00000454244 | P2 | ||
VPS9D1 | ENST00000565023.1 | c.373T>C | p.Cys125Arg | missense_variant | 3/6 | 5 | ENSP00000455792 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD3 exomes AF: 0.00000412 AC: 1AN: 242602Hom.: 0 AF XY: 0.00000752 AC XY: 1AN XY: 133016
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GnomAD4 exome AF: 0.0000726 AC: 106AN: 1459618Hom.: 0 Cov.: 33 AF XY: 0.0000689 AC XY: 50AN XY: 726128
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GnomAD4 genome Cov.: 31
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31
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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 | Oct 13, 2021 | The c.1570T>C (p.C524R) alteration is located in exon 12 (coding exon 12) of the VPS9D1 gene. This alteration results from a T to C substitution at nucleotide position 1570, causing the cysteine (C) at amino acid position 524 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
1.0
.;D
Vest4
MutPred
0.76
.;Gain of sheet (P = 0.0149);
MVP
MPC
0.91
ClinPred
D
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