9-77307991-A-G

Variant summary

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

The NM_033305.3(VPS13A):ā€‹c.4007A>Gā€‹(p.His1336Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,450,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H1336L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000062 ( 0 hom. )

Consequence

VPS13A
NM_033305.3 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.09
Variant links:
Genes affected
VPS13A (HGNC:1908): (vacuolar protein sorting 13 homolog A) The protein encoded by this gene may control steps in the cycling of proteins through the trans-Golgi network to endosomes, lysosomes and the plasma membrane. Mutations in this gene cause the autosomal recessive disorder, chorea-acanthocytosis. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]

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=0.10589728).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
VPS13ANM_033305.3 linkuse as main transcriptc.4007A>G p.His1336Arg missense_variant 35/72 ENST00000360280.8
VPS13ANM_001018037.2 linkuse as main transcriptc.3890A>G p.His1297Arg missense_variant 34/71
VPS13ANM_015186.4 linkuse as main transcriptc.4007A>G p.His1336Arg missense_variant 35/69
VPS13ANM_001018038.3 linkuse as main transcriptc.4007A>G p.His1336Arg missense_variant 35/69

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
VPS13AENST00000360280.8 linkuse as main transcriptc.4007A>G p.His1336Arg missense_variant 35/721 NM_033305.3 P4Q96RL7-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
250952
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135620
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:
0.00
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.00000620
AC:
9
AN:
1450738
Hom.:
0
Cov.:
32
AF XY:
0.00000415
AC XY:
3
AN XY:
722484
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:
0.00000817
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.075
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.66
CADD
Benign
19
DANN
Benign
0.96
DEOGEN2
Benign
0.17
.;.;T;.;.;.;T
Eigen
Benign
-0.22
Eigen_PC
Benign
-0.012
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.74
.;T;.;.;T;T;T
M_CAP
Benign
0.0082
T
MetaRNN
Benign
0.11
T;T;T;T;T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.2
L;.;L;L;L;L;L
MutationTaster
Benign
0.70
N;N;N;N
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-0.71
N;N;N;N;.;.;.
REVEL
Benign
0.066
Sift
Benign
0.34
T;T;T;T;.;.;.
Sift4G
Benign
0.34
T;T;T;T;.;.;.
Polyphen
0.10
B;B;B;B;B;B;B
Vest4
0.24
MutPred
0.52
Gain of solvent accessibility (P = 0.0584);.;Gain of solvent accessibility (P = 0.0584);Gain of solvent accessibility (P = 0.0584);Gain of solvent accessibility (P = 0.0584);Gain of solvent accessibility (P = 0.0584);Gain of solvent accessibility (P = 0.0584);
MVP
0.47
MPC
0.16
ClinPred
0.25
T
GERP RS
4.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.11
gMVP
0.39

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: rs142058362; hg19: chr9-79922907; API