rs587780468
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006950.3(SYN1):āc.1621G>Cā(p.Gly541Arg) 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. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 23)
Exomes š: 0.0 ( 0 hom. 0 hem. )
Failed GnomAD Quality Control
Consequence
SYN1
NM_006950.3 missense
NM_006950.3 missense
Scores
1
3
13
Clinical Significance
Conservation
PhyloP100: 1.90
Genes affected
SYN1 (HGNC:11494): (synapsin I) 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. This member of the synapsin family plays a role in regulation of axonogenesis and synaptogenesis. The protein encoded serves as a substrate for several different protein kinases and phosphorylation may function in the regulation of this protein in the nerve terminal. Mutations in this gene may be associated with X-linked disorders with primary neuronal degeneration such as Rett syndrome. Alternatively spliced transcript variants encoding different isoforms have been identified. [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=0.14138553).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYN1 | NM_006950.3 | c.1621G>C | p.Gly541Arg | missense_variant | 12/13 | ENST00000295987.13 | |
SYN1 | NM_133499.2 | c.1621G>C | p.Gly541Arg | missense_variant | 12/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYN1 | ENST00000295987.13 | c.1621G>C | p.Gly541Arg | missense_variant | 12/13 | 2 | NM_006950.3 | P3 | |
SYN1 | ENST00000340666.5 | c.1621G>C | p.Gly541Arg | missense_variant | 12/13 | 1 | A1 | ||
SYN1 | ENST00000640721.1 | c.70+325G>C | intron_variant | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 912155Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 284483
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
912155
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
284483
Gnomad4 AFR exome
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Gnomad4 AMR exome
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Gnomad4 SAS exome
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Gnomad4 FIN exome
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Gnomad4 OTH exome
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GnomAD4 genome ? Cov.: 23
GnomAD4 genome
?
Cov.:
23
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Sep 10, 2013 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N
MutationTaster
Benign
N;N
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;D
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MutPred
Gain of methylation at G541 (P = 0.0085);Gain of methylation at G541 (P = 0.0085);
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