rs1267724404

Variant summary

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

The NM_004913.3(VPS9D1):ā€‹c.1549G>Cā€‹(p.Gly517Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,611,132 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 31)
Exomes š‘“: 0.0000041 ( 0 hom. )

Consequence

VPS9D1
NM_004913.3 missense

Scores

3
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.990
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=0.20511141).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
VPS9D1NM_004913.3 linkc.1549G>C p.Gly517Arg 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.1549G>C p.Gly517Arg missense_variant Exon 12 of 15 1 NM_004913.3 ENSP00000374037.3 Q9Y2B5-1
VPS9D1ENST00000561976.5 linkc.1339G>C p.Gly447Arg missense_variant Exon 11 of 14 1 ENSP00000454244.1 H3BM58
VPS9D1ENST00000565023.1 linkc.349G>C p.Gly117Arg missense_variant Exon 3 of 6 5 ENSP00000455792.1 H3BQI2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152132
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000826
AC:
2
AN:
242032
Hom.:
0
AF XY:
0.0000151
AC XY:
2
AN XY:
132622
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000185
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000411
AC:
6
AN:
1459000
Hom.:
0
Cov.:
32
AF XY:
0.00000551
AC XY:
4
AN XY:
725868
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:
0.00000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152132
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
74314
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.35
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
17
DANN
Benign
0.53
DEOGEN2
Benign
0.012
.;T
Eigen
Benign
-0.22
Eigen_PC
Benign
-0.21
FATHMM_MKL
Benign
0.13
N
LIST_S2
Uncertain
0.87
D;D
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.21
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.2
.;L
PrimateAI
Uncertain
0.69
T
PROVEAN
Benign
-0.090
N;N
REVEL
Benign
0.14
Sift
Benign
0.73
T;T
Sift4G
Benign
0.60
T;T
Polyphen
0.95
.;P
Vest4
0.32
MutPred
0.63
.;Gain of solvent accessibility (P = 0.0171);
MVP
0.27
MPC
0.27
ClinPred
0.18
T
GERP RS
5.1
Varity_R
0.13
gMVP
0.36

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: rs1267724404; hg19: chr16-89775683; API