16-89708911-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004913.3(VPS9D1):​c.1643C>G​(p.Pro548Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 34)

Consequence

VPS9D1
NM_004913.3 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.247
Variant links:
Genes affected
VPS9D1 (HGNC:13526): (VPS9 domain containing 1) Enables identical protein binding activity. Predicted to be involved in ATP synthesis coupled proton transport. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.021991044).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
VPS9D1NM_004913.3 linkc.1643C>G p.Pro548Arg missense_variant Exon 13 of 15 ENST00000389386.8 NP_004904.2 Q9Y2B5-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
VPS9D1ENST00000389386.8 linkc.1643C>G p.Pro548Arg missense_variant Exon 13 of 15 1 NM_004913.3 ENSP00000374037.3 Q9Y2B5-1
VPS9D1ENST00000561976.5 linkc.1433C>G p.Pro478Arg missense_variant Exon 12 of 14 1 ENSP00000454244.1 H3BM58
VPS9D1ENST00000565023.1 linkc.443C>G p.Pro148Arg missense_variant Exon 4 of 6 5 ENSP00000455792.1 H3BQI2

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.058
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
4.0
DANN
Benign
0.65
DEOGEN2
Benign
0.0072
.;T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.0034
N
LIST_S2
Benign
0.49
T;T
M_CAP
Benign
0.0024
T
MetaRNN
Benign
0.022
T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
-2.1
.;N
PrimateAI
Benign
0.47
T
PROVEAN
Benign
1.1
N;N
REVEL
Benign
0.019
Sift
Benign
0.56
T;T
Sift4G
Benign
0.77
T;T
Polyphen
0.0
.;B
Vest4
0.056
MutPred
0.42
.;Loss of glycosylation at P548 (P = 0.0255);
MVP
0.16
MPC
0.19
ClinPred
0.040
T
GERP RS
2.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.026
gMVP
0.15

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs975544237; hg19: chr16-89775319; API