5-76209872-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_014979.4(SV2C):c.898A>G(p.Ile300Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,461,118 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 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000011 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
SV2C
NM_014979.4 missense
NM_014979.4 missense
Scores
1
5
13
Clinical Significance
Conservation
PhyloP100: 9.21
Genes affected
SV2C (HGNC:30670): (synaptic vesicle glycoprotein 2C) Predicted to enable transmembrane transporter activity. Predicted to be involved in chemical synaptic transmission; neurotransmitter transport; and transmembrane transport. Predicted to be located in plasma membrane and synaptic vesicle. Predicted to be active in neuron projection and synaptic vesicle membrane. Predicted to be integral component of synaptic vesicle membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.4016776).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SV2C | NM_014979.4 | c.898A>G | p.Ile300Val | missense_variant | 4/13 | ENST00000502798.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SV2C | ENST00000502798.7 | c.898A>G | p.Ile300Val | missense_variant | 4/13 | 1 | NM_014979.4 | P1 | |
SV2C | ENST00000322285.7 | c.898A>G | p.Ile300Val | missense_variant | 4/13 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152232Hom.: 0 Cov.: 33
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000242 AC: 6AN: 248324Hom.: 0 AF XY: 0.0000298 AC XY: 4AN XY: 134454
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GnomAD4 exome AF: 0.0000110 AC: 16AN: 1461118Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 726798
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GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.00000656 AC: 1AN: 152350Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74484
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?
Data not reliable, filtered out with message: AS_VQSR
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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 | Sep 23, 2023 | The c.898A>G (p.I300V) alteration is located in exon 4 (coding exon 3) of the SV2C gene. This alteration results from a A to G substitution at nucleotide position 898, causing the isoleucine (I) at amino acid position 300 to be replaced by a valine (V). 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
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
P;.
Vest4
MutPred
Loss of catalytic residue at P302 (P = 0.0271);Loss of catalytic residue at P302 (P = 0.0271);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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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