chr2-85591782-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006634.3(VAMP5):c.61C>T(p.Arg21Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,614,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000034 ( 0 hom. )
Consequence
VAMP5
NM_006634.3 missense
NM_006634.3 missense
Scores
2
6
11
Clinical Significance
Conservation
PhyloP100: 2.90
Genes affected
VAMP5 (HGNC:12646): (vesicle associated membrane protein 5) Synaptobrevins/VAMPs, syntaxins, and the 25-kD synaptosomal-associated protein are the main components of a protein complex involved in the docking and/or fusion of vesicles and cell membranes. The VAMP5 gene is a member of the vesicle-associated membrane protein (VAMP)/synaptobrevin family and the SNARE superfamily. This VAMP family member may participate in vesicle trafficking events that are associated with myogenesis. [provided by RefSeq, Jul 2008]
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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=0.21597561).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VAMP5 | NM_006634.3 | c.61C>T | p.Arg21Cys | missense_variant | 2/3 | ENST00000306384.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VAMP5 | ENST00000306384.5 | c.61C>T | p.Arg21Cys | missense_variant | 2/3 | 1 | NM_006634.3 | P1 | |
VAMP5 | ENST00000462451.1 | n.186C>T | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152154Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000597 AC: 15AN: 251460Hom.: 0 AF XY: 0.0000809 AC XY: 11AN XY: 135904
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GnomAD4 exome AF: 0.0000335 AC: 49AN: 1461858Hom.: 0 Cov.: 32 AF XY: 0.0000330 AC XY: 24AN XY: 727232
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GnomAD4 genome AF: 0.0000460 AC: 7AN: 152154Hom.: 0 Cov.: 31 AF XY: 0.0000538 AC XY: 4AN XY: 74320
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 24, 2024 | The c.61C>T (p.R21C) alteration is located in exon 2 (coding exon 2) of the VAMP5 gene. This alteration results from a C to T substitution at nucleotide position 61, causing the arginine (R) at amino acid position 21 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Loss of MoRF binding (P = 0.0031);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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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