rs193920952
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001323032.3(SV2B):c.1537C>T(p.Arg513Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,614,078 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000018 ( 0 hom. )
Consequence
SV2B
NM_001323032.3 missense
NM_001323032.3 missense
Scores
1
7
9
Clinical Significance
Conservation
PhyloP100: 3.12
Genes affected
SV2B (HGNC:16874): (synaptic vesicle glycoprotein 2B) This gene encodes a member of the synaptic vesicle proteins 2 (SV2) family and major facilitator superfamily of proteins. This protein and other members of the family are localized to synaptic vesicles and may function in the regulation of vesicle trafficking and exocytosis. Studies in mice suggest that the encoded protein may act as a protein receptor for botulinum neurotoxin E in neurons, and that this protein may be important for the integrity of the glomerular filtration barrier. This gene shows reduced expression in areas of synaptic loss in the hippocampus of human temporal lobe epilepsy patients. [provided by RefSeq, Sep 2016]
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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 |
---|---|---|---|---|---|---|---|
SV2B | NM_001323032.3 | c.1537C>T | p.Arg513Trp | missense_variant | 11/13 | ENST00000394232.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SV2B | ENST00000394232.6 | c.1537C>T | p.Arg513Trp | missense_variant | 11/13 | 5 | NM_001323032.3 | P1 | |
SV2B | ENST00000330276.4 | c.1537C>T | p.Arg513Trp | missense_variant | 10/12 | 1 | P1 | ||
SV2B | ENST00000557410.5 | c.1537C>T | p.Arg513Trp | missense_variant, NMD_transcript_variant | 12/15 | 1 | |||
SV2B | ENST00000545111.6 | c.1084C>T | p.Arg362Trp | missense_variant | 10/12 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152208Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251382Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135896
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GnomAD4 exome AF: 0.0000178 AC: 26AN: 1461870Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10AN XY: 727232
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152208Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74366
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Malignant tumor of prostate Uncertain:1
Uncertain significance, no assertion criteria provided | literature only | Science for Life laboratory, Karolinska Institutet | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;.;D
M_CAP
Benign
T
MetaRNN
Uncertain
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
1.0
.;D;D
Vest4
MutPred
0.67
.;Gain of ubiquitination at K508 (P = 0.1245);Gain of ubiquitination at K508 (P = 0.1245);
MVP
MPC
0.92
ClinPred
D
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