chr16-89708482-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004913.3(VPS9D1):​c.1747G>A​(p.Gly583Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000936 in 1,613,138 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000099 ( 0 hom. )

Consequence

VPS9D1
NM_004913.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.43
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.21760657).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
VPS9D1NM_004913.3 linkuse as main transcriptc.1747G>A p.Gly583Ser missense_variant 14/15 ENST00000389386.8 NP_004904.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
VPS9D1ENST00000389386.8 linkuse as main transcriptc.1747G>A p.Gly583Ser missense_variant 14/151 NM_004913.3 ENSP00000374037 A2Q9Y2B5-1
VPS9D1ENST00000561976.5 linkuse as main transcriptc.1537G>A p.Gly513Ser missense_variant 13/141 ENSP00000454244 P2
VPS9D1ENST00000565023.1 linkuse as main transcriptc.550G>A p.Gly184Ser missense_variant 5/65 ENSP00000455792

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152244
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000126
AC:
31
AN:
245328
Hom.:
0
AF XY:
0.0000971
AC XY:
13
AN XY:
133904
show subpopulations
Gnomad AFR exome
AF:
0.0000661
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000558
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000217
Gnomad OTH exome
AF:
0.000167
GnomAD4 exome
AF:
0.0000986
AC:
144
AN:
1460776
Hom.:
0
Cov.:
32
AF XY:
0.0000949
AC XY:
69
AN XY:
726706
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.000134
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000190
Gnomad4 NFE exome
AF:
0.000117
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
AF:
0.0000459
AC:
7
AN:
152362
Hom.:
0
Cov.:
34
AF XY:
0.0000537
AC XY:
4
AN XY:
74502
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000965
Hom.:
0
Bravo
AF:
0.0000567
ExAC
AF:
0.000141
AC:
17
EpiCase
AF:
0.00
EpiControl
AF:
0.000178

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 submitterclinical testingAmbry GeneticsAug 30, 2022The c.1747G>A (p.G583S) alteration is located in exon 14 (coding exon 14) of the VPS9D1 gene. This alteration results from a G to A substitution at nucleotide position 1747, causing the glycine (G) at amino acid position 583 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.47
CADD
Uncertain
24
DANN
Uncertain
0.98
DEOGEN2
Benign
0.012
.;T
Eigen
Benign
0.022
Eigen_PC
Benign
0.032
FATHMM_MKL
Benign
0.35
N
LIST_S2
Benign
0.83
T;T
M_CAP
Benign
0.0098
T
MetaRNN
Benign
0.22
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.9
.;L
MutationTaster
Benign
0.98
N;N
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-0.65
N;N
REVEL
Benign
0.054
Sift
Benign
0.27
T;T
Sift4G
Benign
0.63
T;T
Polyphen
0.82
.;P
Vest4
0.47
MVP
0.68
MPC
0.21
ClinPred
0.028
T
GERP RS
3.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.050
gMVP
0.18

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: rs777363379; hg19: chr16-89774890; API