rs1011100710

Variant summary

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

The NM_004913.3(VPS9D1):​c.23G>T​(p.Gly8Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000021 in 1,426,464 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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: 𝑓 0.0000066 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

VPS9D1
NM_004913.3 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.596
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]
ZNF276 (HGNC:23330): (zinc finger protein 276) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in kinetochore. [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=0.08455637).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
VPS9D1NM_004913.3 linkc.23G>T p.Gly8Val missense_variant Exon 1 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.23G>T p.Gly8Val missense_variant Exon 1 of 15 1 NM_004913.3 ENSP00000374037.3 Q9Y2B5-1
VPS9D1ENST00000563798.1 linkn.23G>T non_coding_transcript_exon_variant Exon 1 of 6 3 ENSP00000454889.1 H3BNK1
ZNF276ENST00000562530.5 linkn.-21+257C>A intron_variant Intron 1 of 10 2 ENSP00000455466.1 H3BPT7

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152076
Hom.:
0
Cov.:
34
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
GnomAD4 exome
AF:
0.00000157
AC:
2
AN:
1274388
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
626742
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:
0.00000197
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152076
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
74304
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
Benign
0.11
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
20
DANN
Benign
0.85
DEOGEN2
Benign
0.033
T
Eigen
Benign
-0.88
Eigen_PC
Benign
-0.88
FATHMM_MKL
Benign
0.013
N
LIST_S2
Benign
0.51
T
M_CAP
Pathogenic
0.86
D
MetaRNN
Benign
0.085
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
-2.1
N
REVEL
Benign
0.0030
Sift
Benign
0.24
T
Sift4G
Benign
0.18
T
Polyphen
0.028
B
Vest4
0.068
MutPred
0.33
Loss of relative solvent accessibility (P = 0.0186);
MVP
0.014
MPC
0.22
ClinPred
0.13
T
GERP RS
1.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.14
gMVP
0.16

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: rs1011100710; hg19: chr16-89787247; API