chr20-58389497-A-C
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4
The NM_004738.5(VAPB):c.38A>C(p.Gln13Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
VAPB
NM_004738.5 missense
NM_004738.5 missense
Scores
2
2
15
Clinical Significance
Conservation
PhyloP100: 3.02
Genes affected
VAPB (HGNC:12649): (VAMP associated protein B and C) The protein encoded by this gene is a type IV membrane protein found in plasma and intracellular vesicle membranes. The encoded protein is found as a homodimer and as a heterodimer with VAPA. This protein also can interact with VAMP1 and VAMP2 and may be involved in vesicle trafficking. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM1
In a domain MSP (size 117) in uniprot entity VAPB_HUMAN there are 4 pathogenic changes around while only 1 benign (80%) in NM_004738.5
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.32470024).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VAPB | NM_004738.5 | c.38A>C | p.Gln13Pro | missense_variant | 1/6 | ENST00000475243.6 | |
VAPB | NM_001195677.2 | c.38A>C | p.Gln13Pro | missense_variant | 1/3 | ||
VAPB | NR_036633.2 | n.269A>C | non_coding_transcript_exon_variant | 1/4 | |||
VAPB | XR_001754433.3 | n.269A>C | non_coding_transcript_exon_variant | 1/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VAPB | ENST00000475243.6 | c.38A>C | p.Gln13Pro | missense_variant | 1/6 | 1 | NM_004738.5 | P1 | |
VAPB | ENST00000395802.7 | c.38A>C | p.Gln13Pro | missense_variant | 1/3 | 1 | |||
VAPB | ENST00000265619.6 | n.123A>C | non_coding_transcript_exon_variant | 1/6 | 2 | ||||
VAPB | ENST00000520497.1 | c.38A>C | p.Gln13Pro | missense_variant, NMD_transcript_variant | 1/4 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Amyotrophic lateral sclerosis type 8;C1854058:Adult-onset proximal spinal muscular atrophy, autosomal dominant Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 22, 2023 | ClinVar contains an entry for this variant (Variation ID: 1062695). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant  is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant has not been reported in the literature in individuals affected with VAPB-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 13 of the VAPB protein (p.Gln13Pro). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MutPred
Gain of catalytic residue at P12 (P = 0.0243);Gain of catalytic residue at P12 (P = 0.0243);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.