rs795010

Positions:

• chr3-12167495-T-A
• chr3-12167495-T-C
• chr3-12167495-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133625.6(SYN2):​c.1055+187T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.723 in 152,026 control chromosomes in the GnomAD database, including 40,115 homozygotes. 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: 𝑓 0.72 (40115 hom., cov: 31)
• Consequence: SYN2 NM_133625.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0670

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYN2	NM_133625.6	c.1055+187T>A		intron_variant		ENST00000621198.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYN2	ENST00000621198.5	c.1055+187T>A		intron_variant		1	NM_133625.6	P2

Frequencies

GnomAD3 genomes AF: 0.724 AC: 109908 AN: 151906 Hom.: 40083 Cov.: 31

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.911

Gnomad AMR AF: 0.795

Gnomad ASJ AF: 0.729

Gnomad EAS AF: 0.681

Gnomad SAS AF: 0.789

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.749

Gnomad OTH AF: 0.757

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.723 AC: 109985 AN: 152026 Hom.: 40115 Cov.: 31 AF XY: 0.728 AC XY: 54073 AN XY: 74326

Gnomad4 AFR AF: 0.629

Gnomad4 AMR AF: 0.795

Gnomad4 ASJ AF: 0.729

Gnomad4 EAS AF: 0.681

Gnomad4 SAS AF: 0.789

Gnomad4 FIN AF: 0.788

Gnomad4 NFE AF: 0.749

Gnomad4 OTH AF: 0.758

Alfa AF: 0.734 Hom.: 5111

Bravo AF: 0.720

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	5.8
DANN	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs795010; hg19: chr3-12208995;