16-89709418-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004913.3(VPS9D1):ā€‹c.1406G>Cā€‹(p.Arg469Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000147 in 1,364,524 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes š‘“: 0.0000015 ( 0 hom. )

Consequence

VPS9D1
NM_004913.3 missense

Scores

7
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.798
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]

Genome browser will be placed here

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 rank MANE Protein UniProt
VPS9D1NM_004913.3 linkc.1406G>C p.Arg469Pro missense_variant Exon 12 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.1406G>C p.Arg469Pro missense_variant Exon 12 of 15 1 NM_004913.3 ENSP00000374037.3 Q9Y2B5-1
VPS9D1ENST00000561976.5 linkc.1196G>C p.Arg399Pro missense_variant Exon 11 of 14 1 ENSP00000454244.1 H3BM58
VPS9D1ENST00000565023.1 linkc.206G>C p.Arg69Pro missense_variant Exon 3 of 6 5 ENSP00000455792.1 H3BQI2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000147
AC:
2
AN:
1364524
Hom.:
0
Cov.:
32
AF XY:
0.00000298
AC XY:
2
AN XY:
670428
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000187
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.36
BayesDel_addAF
Benign
-0.011
T
BayesDel_noAF
Benign
-0.25
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Benign
0.32
.;T
Eigen
Benign
-0.0082
Eigen_PC
Benign
-0.17
FATHMM_MKL
Benign
0.35
N
LIST_S2
Benign
0.80
T;T
M_CAP
Benign
0.064
D
MetaRNN
Uncertain
0.73
D;D
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.8
.;M
PrimateAI
Benign
0.44
T
PROVEAN
Uncertain
-3.3
D;D
REVEL
Benign
0.24
Sift
Uncertain
0.019
D;D
Sift4G
Uncertain
0.0040
D;D
Polyphen
0.99
.;D
Vest4
0.74
MutPred
0.54
.;Gain of loop (P = 0.002);
MVP
0.54
MPC
0.52
ClinPred
0.98
D
GERP RS
2.1
Varity_R
0.70
gMVP
0.82

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs768244692; hg19: chr16-89775826; API