chr16-89710958-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004913.3(VPS9D1):āc.886T>Cā(p.Tyr296His) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,456,410 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 33)
Exomes š: 0.0000015 ( 0 hom. )
Consequence
VPS9D1
NM_004913.3 missense
NM_004913.3 missense
Scores
3
6
10
Clinical Significance
Conservation
PhyloP100: 4.34
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
VPS9D1 | NM_004913.3 | c.886T>C | p.Tyr296His | missense_variant | 10/15 | ENST00000389386.8 | NP_004904.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
VPS9D1 | ENST00000389386.8 | c.886T>C | p.Tyr296His | missense_variant | 10/15 | 1 | NM_004913.3 | ENSP00000374037 | A2 | |
VPS9D1 | ENST00000561976.5 | c.676T>C | p.Tyr226His | missense_variant | 9/14 | 1 | ENSP00000454244 | P2 | ||
VPS9D1 | ENST00000568691.5 | n.813T>C | non_coding_transcript_exon_variant | 6/6 | 3 | |||||
VPS9D1 | ENST00000565452.1 | downstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152158Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.00000153 AC: 2AN: 1304252Hom.: 0 Cov.: 33 AF XY: 0.00000157 AC XY: 1AN XY: 635110
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152158Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74334
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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 | Apr 25, 2023 | The c.886T>C (p.Y296H) alteration is located in exon 10 (coding exon 10) of the VPS9D1 gene. This alteration results from a T to C substitution at nucleotide position 886, causing the tyrosine (Y) at amino acid position 296 to be replaced by a histidine (H). 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
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
.;T
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Pathogenic
D;D
Sift4G
Uncertain
D;D
Polyphen
1.0
.;D
Vest4
MutPred
0.55
.;Gain of disorder (P = 0.0247);
MVP
MPC
0.82
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