chr16-89709864-T-G
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_004913.3(VPS9D1):āc.1301A>Cā(p.Asn434Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000539 in 1,613,410 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.00019 ( 0 hom., cov: 32)
Exomes š: 0.00057 ( 2 hom. )
Consequence
VPS9D1
NM_004913.3 missense
NM_004913.3 missense
Scores
10
9
Clinical Significance
Conservation
PhyloP100: 2.22
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.27453983).
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
VPS9D1 | NM_004913.3 | c.1301A>C | p.Asn434Thr | 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.1301A>C | p.Asn434Thr | missense_variant | 11/15 | 1 | NM_004913.3 | ENSP00000374037 | A2 | |
VPS9D1 | ENST00000561976.5 | c.1091A>C | p.Asn364Thr | missense_variant | 10/14 | 1 | ENSP00000454244 | P2 | ||
VPS9D1 | ENST00000565023.1 | c.104A>C | p.Asn35Thr | missense_variant | 2/6 | 5 | ENSP00000455792 |
Frequencies
GnomAD3 genomes AF: 0.000191 AC: 29AN: 152164Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000165 AC: 41AN: 248738Hom.: 0 AF XY: 0.000126 AC XY: 17AN XY: 134972
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GnomAD4 exome AF: 0.000575 AC: 840AN: 1461246Hom.: 2 Cov.: 31 AF XY: 0.000538 AC XY: 391AN XY: 726952
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GnomAD4 genome AF: 0.000191 AC: 29AN: 152164Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74340
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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 | Jan 10, 2023 | The c.1301A>C (p.N434T) alteration is located in exon 11 (coding exon 11) of the VPS9D1 gene. This alteration results from a A to C substitution at nucleotide position 1301, causing the asparagine (N) at amino acid position 434 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
Uncertain
DEOGEN2
Benign
.;T
Eigen
Uncertain
Eigen_PC
Uncertain
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
Uncertain
D;D
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
0.84
.;P
Vest4
MVP
MPC
0.58
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