NM_133625.6:c.-259G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_133625.6(SYN2):​c.-259G>A variant causes a upstream gene 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 26)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

SYN2
NM_133625.6 upstream_gene

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.128

Publications

0 publications found
Variant links:
Genes affected
SYN2 (HGNC:11495): (synapsin II) 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 encodes a neuron-specific phosphoprotein that selectively binds to small synaptic vesicles in the presynaptic nerve terminal. Polymorphisms in this gene are associated with abnormal presynaptic function and related neuronal disorders, including autism, epilepsy, bipolar disorder and schizophrenia. Alternative splicing of this gene results in multiple transcript variants. The tissue inhibitor of metalloproteinase 4 gene is located within an intron of this gene and is transcribed in the opposite direction. [provided by RefSeq, Feb 2014]

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.63).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SYN2NM_133625.6 linkc.-259G>A upstream_gene_variant ENST00000621198.5 NP_598328.1 Q92777-1Q86VA8B3KRB3
SYN2NM_003178.6 linkc.-259G>A upstream_gene_variant NP_003169.2 Q92777-2Q59GM1
SYN2XM_006713311.4 linkc.-259G>A upstream_gene_variant XP_006713374.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SYN2ENST00000621198.5 linkc.-259G>A upstream_gene_variant 1 NM_133625.6 ENSP00000480050.1 Q92777-1
SYN2ENST00000620175.4 linkc.-259G>A upstream_gene_variant 1 ENSP00000484916.1 Q92777-2

Frequencies

GnomAD3 genomes
Cov.:
26
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
2998
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
1622
African (AFR)
AF:
0.00
AC:
0
AN:
224
American (AMR)
AF:
0.00
AC:
0
AN:
50
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
108
East Asian (EAS)
AF:
0.00
AC:
0
AN:
450
South Asian (SAS)
AF:
0.00
AC:
0
AN:
96
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
98
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
26
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1774
Other (OTH)
AF:
0.00
AC:
0
AN:
172
GnomAD4 genome
Cov.:
26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.63
CADD
Benign
5.5
DANN
Benign
0.96
PhyloP100
-0.13
PromoterAI
-0.16
Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs2623873; hg19: chr3-12045767; API