rs755454094
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_033305.3(VPS13A):c.4826C>T(p.Pro1609Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000211 in 1,612,834 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P1609P) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000021 ( 0 hom. )
Consequence
VPS13A
NM_033305.3 missense
NM_033305.3 missense
Scores
1
11
5
Clinical Significance
Conservation
PhyloP100: 4.79
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]
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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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VPS13A | NM_033305.3 | c.4826C>T | p.Pro1609Leu | missense_variant | 39/72 | ENST00000360280.8 | |
VPS13A | NM_001018037.2 | c.4709C>T | p.Pro1570Leu | missense_variant | 38/71 | ||
VPS13A | NM_015186.4 | c.4826C>T | p.Pro1609Leu | missense_variant | 39/69 | ||
VPS13A | NM_001018038.3 | c.4826C>T | p.Pro1609Leu | missense_variant | 39/69 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VPS13A | ENST00000360280.8 | c.4826C>T | p.Pro1609Leu | missense_variant | 39/72 | 1 | NM_033305.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 151964Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 250844Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135562
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GnomAD4 exome AF: 0.0000212 AC: 31AN: 1460870Hom.: 0 Cov.: 30 AF XY: 0.0000138 AC XY: 10AN XY: 726730
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 151964Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74214
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Feb 07, 2017 | - - |
Chorea-acanthocytosis Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 11, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;M;M;M;M;M
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D;.;.;.
REVEL
Benign
Sift
Uncertain
D;D;D;D;.;.;.
Sift4G
Uncertain
D;D;D;D;.;.;.
Polyphen
D;P;D;D;D;D;D
Vest4
MutPred
Gain of sheet (P = 0.039);.;Gain of sheet (P = 0.039);Gain of sheet (P = 0.039);Gain of sheet (P = 0.039);Gain of sheet (P = 0.039);Gain of sheet (P = 0.039);
MVP
MPC
0.57
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at