rs372082040

Variant summary

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

The NM_004913.3(VPS9D1):​c.1774G>T​(p.Ala592Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,390 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: 34)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

VPS9D1
NM_004913.3 missense

Scores

8
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.69
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.1774G>T p.Ala592Ser missense_variant Exon 14 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.1774G>T p.Ala592Ser missense_variant Exon 14 of 15 1 NM_004913.3 ENSP00000374037.3 Q9Y2B5-1
VPS9D1ENST00000561976.5 linkc.1564G>T p.Ala522Ser missense_variant Exon 13 of 14 1 ENSP00000454244.1 H3BM58
VPS9D1ENST00000565023.1 linkc.574G>T p.Ala192Ser missense_variant Exon 5 of 6 5 ENSP00000455792.1 H3BQI2

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460390
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
726488
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.066
T
BayesDel_noAF
Benign
-0.33
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.057
.;T
Eigen
Uncertain
0.49
Eigen_PC
Uncertain
0.47
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Benign
0.84
T;T
M_CAP
Benign
0.021
T
MetaRNN
Uncertain
0.50
D;D
MetaSVM
Benign
-0.98
T
MutationAssessor
Uncertain
2.4
.;M
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
-0.77
N;N
REVEL
Benign
0.28
Sift
Benign
0.25
T;T
Sift4G
Uncertain
0.023
D;D
Polyphen
1.0
.;D
Vest4
0.56
MutPred
0.47
.;Gain of relative solvent accessibility (P = 0.0479);
MVP
0.69
MPC
0.23
ClinPred
0.97
D
GERP RS
5.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.14
gMVP
0.49

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-89774863; API