chr22-32518235-G-C
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong
The NM_003490.4(SYN3):c.1418C>G(p.Ser473Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000731 in 1,613,744 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000077 ( 1 hom. )
Consequence
SYN3
NM_003490.4 missense
NM_003490.4 missense
Scores
1
4
14
Clinical Significance
Conservation
PhyloP100: 7.64
Publications
0 publications found
Genes affected
SYN3 (HGNC:11496): (synapsin III) This gene is a member of the synapsin gene family. Synapsins encode neuronal phosphoproteins which associate with the cytoplasmic surface of synaptic vesicles. Family members are characterized by common protein domains, and they are implicated in synaptogenesis and the modulation of neurotransmitter release, suggesting a potential role in several neuropsychiatric diseases. The protein encoded by this gene shares the synapsin family domain model, with domains A, C, and E exhibiting the highest degree of conservation. The protein contains a unique domain J, located between domains C and E. Based on this gene's localization to 22q12.3, a possible schizophrenia susceptibility locus, and the established neurobiological roles of the synapsins, this family member may represent a candidate gene for schizophrenia. The TIMP3 gene is located within an intron of this gene and is transcribed in the opposite direction. Alternative splicing of this gene results in multiple splice variants that encode different isoforms. [provided by RefSeq, Oct 2008]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -4 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.06648421).
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| SYN3 | NM_003490.4 | c.1418C>G | p.Ser473Cys | missense_variant | Exon 13 of 14 | ENST00000358763.7 | NP_003481.3 |
Ensembl
Frequencies
GnomAD3 genomes 0.0000394 AC: 6AN: 152130Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
6
AN:
152130
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.000160 AC: 40AN: 249950 AF XY: 0.000200 show subpopulations
GnomAD2 exomes
AF:
AC:
40
AN:
249950
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000766 AC: 112AN: 1461614Hom.: 1 Cov.: 31 AF XY: 0.000105 AC XY: 76AN XY: 727082 show subpopulations
GnomAD4 exome
AF:
AC:
112
AN:
1461614
Hom.:
Cov.:
31
AF XY:
AC XY:
76
AN XY:
727082
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33474
American (AMR)
AF:
AC:
1
AN:
44718
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26128
East Asian (EAS)
AF:
AC:
0
AN:
39694
South Asian (SAS)
AF:
AC:
75
AN:
86228
European-Finnish (FIN)
AF:
AC:
0
AN:
53322
Middle Eastern (MID)
AF:
AC:
5
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
24
AN:
1111898
Other (OTH)
AF:
AC:
7
AN:
60384
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
7
14
21
28
35
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.0000394 AC: 6AN: 152130Hom.: 0 Cov.: 32 AF XY: 0.0000808 AC XY: 6AN XY: 74300 show subpopulations
GnomAD4 genome
AF:
AC:
6
AN:
152130
Hom.:
Cov.:
32
AF XY:
AC XY:
6
AN XY:
74300
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41418
American (AMR)
AF:
AC:
1
AN:
15276
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5186
South Asian (SAS)
AF:
AC:
1
AN:
4820
European-Finnish (FIN)
AF:
AC:
0
AN:
10616
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
3
AN:
68026
Other (OTH)
AF:
AC:
1
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.492
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
AF:
AC:
22
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Mar 19, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.1418C>G (p.S473C) alteration is located in exon 12 (coding exon 12) of the SYN3 gene. This alteration results from a C to G substitution at nucleotide position 1418, causing the serine (S) at amino acid position 473 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
DANN
Benign
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.
REVEL
Benign
Sift
Uncertain
D;.
Sift4G
Benign
T;T
Polyphen
P;.
Vest4
MutPred
Loss of phosphorylation at S473 (P = 0.0028);.;
MVP
MPC
ClinPred
T
GERP RS
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
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