NM_004913.3:c.1355C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_004913.3(VPS9D1):​c.1355C>G​(p.Ser452Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 32)

Consequence

VPS9D1
NM_004913.3 missense

Scores

1
5
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.90
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 Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.37778044).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
VPS9D1NM_004913.3 linkc.1355C>G p.Ser452Cys missense_variant Exon 11 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.1355C>G p.Ser452Cys missense_variant Exon 11 of 15 1 NM_004913.3 ENSP00000374037.3 Q9Y2B5-1
VPS9D1ENST00000561976.5 linkc.1145C>G p.Ser382Cys missense_variant Exon 10 of 14 1 ENSP00000454244.1 H3BM58
VPS9D1ENST00000565023.1 linkc.155C>G p.Ser52Cys missense_variant Exon 2 of 6 5 ENSP00000455792.1 H3BQI2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.098
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
21
DANN
Uncertain
0.98
DEOGEN2
Benign
0.055
.;T
Eigen
Uncertain
0.36
Eigen_PC
Uncertain
0.35
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.58
T;T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.38
T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Uncertain
2.3
.;M
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
-2.3
N;N
REVEL
Benign
0.19
Sift
Benign
0.071
T;T
Sift4G
Benign
0.12
T;T
Polyphen
0.99
.;D
Vest4
0.38
MutPred
0.45
.;Gain of catalytic residue at S452 (P = 0.0323);
MVP
0.50
MPC
0.17
ClinPred
0.89
D
GERP RS
4.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.14
gMVP
0.27

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: chr16-89776218; COSMIC: COSV101232024; COSMIC: COSV101232024; API